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Your Position: Home > COVID-19 R&D > Accelerated Progress: Spike Protein Mutations on B.1.617 Identified and Studied
Accelerated Progress: Spike Protein Mutations on B.1.617 Identified and Studied
Release time: 2021-05-11 Source: ACROBiosystems Read: 5561

After the sharp rise in COVID-19 cases and deaths in India over recent weeks, at least 20 countries have imposed travel bans and restrictions to and from India. The world again stands at a crossroad of the viral evolution.

When the Indian variants were first reported, scientists were alerted by the simultaneous occurrence of two potent mutations on the viral spike protein, namely E484Q and L452R5, both conferring higher infectivity and immune evasion. Thanks to the accelerated progress of sequence collection and analysis from all over India, much more has now been learned about the combined effect of these two mutations as well as other mutations harbored by the variants, designated B.1.617 by PANGOLIN classification.

Based on a phylogenetic study by Indian Council of Medical Research (ICMR)6, a total of 23 non-synonymous changes at the spike protein were observed from the retrieved sequences, of which 7 common signature mutations were identified (G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H). The study further classified the B.1.617 lineages into three sub-clusters, which differ in their exact mutations. Notably, T95I was shared by a clade of sequences; second H1101D and third V382L, V1175Y (Figure.1.).

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Figure.1. A phylogenetic tree of representative SARS-CoV-2 genomes and the occurring mutations in the spike protein in the sub-clusters pf lineage B.1.617.

Researchers proposed several explanations for the violent spread of B.1.617 in India: 1) both L452R and E484Q have a more stabilizing effect on spike protein that could mediate more efficient binding to human ACE2 receptor, leading to increased host cell entry4; 2) P681R in the S1/S2 furin cleavage site may facilitate more robust proteolytic activation of the spike protein, ensuing enhanced infectivity2; 3) the new combinations of mutations confer stronger immune evasion, e.g. reduced binding by monoclonal antibodies (mAbs) and incompatibility of current vaccines3.

The augmented fitness of B.1.617 was confirmed by neutralizing tests with convalescent or vaccinated sera against the mutated spike protein. In a recent study that appeared in the pre-print repository medRxiv3, plasma from COVID-19 convalescent patients demonstrate diminished neutralization against the variant as compared to the Wuhan WT spike protein, but the reduction in neutralizing capability was limited to 2-fold and less potent than B.1.351 (~6-fold reduction) (Figure.2A.). In the neutralization test with serum from Comirnaty/BNT162b2 (Pfizer–BioNTech vaccine) vaccinated individuals, less efficient inhibition of viral entry mediated by B.1.617 spike protein was observed, but also less pronounced (~3-fold reduction) than that of B.1.351 (>11-fold reduction) (Figure.2B.).


2.jpg

Figure.2A) Diminished neutralization by plasma from COVID-19 convalescent patients against SARS-CoV-2 WT, B.1.351, and B.1.617. 2B) Diminished neutralization by plasma from Comirnaty/BNT162b2 vaccinated patients against SARS-CoV-2 WT, B.1.351, and B.1.617.

Results obtained by ICMR found that recipients of Bharat Biotech's BBV152 (Covaxin) were able to neutralize VUI B.1.617 although with a slightly lower efficacy6.

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Figure.3. Neutralizing response of the individual sera (n=28) vaccinated with BBV152 (Covaxin) collected during phase II clinical trial for the prototype B1 (D614G) (pink), B.1.1.7 (red), B.1.617 (blue).


These preliminary studies yield necessary findings that may help prevent massive transmission of the variant. Certainly, to introduce appropriate public health interventions in the future, continuous genomic surveillance is needed to monitor the mutations on B.1.617 and other emerging variants of SARS-CoV-2.

ACROBiosystems has accelerated the development of B.1.617 recombinant antigens accordingly to help better understand the transmissibility and infectivity of the variant.

Product list
  • India variant

  • S.A. variant

  • UK variant

  • Brazil variant

  • California variant

  • other S & N mutants

MoleculeCat.No.TagHostProduct descriptionSpeciesPreorder/Order
Spike RBDSPD-C52HvHis TagHEK293SARS-CoV-2 Spike RBD (L452R, E484Q), His TagB.1.617

Preorder

Spike RBDSPD-C82EcHis Tag & Avi TagHEK293Biotinylated SARS-CoV-2 Spike RBD (L452R, E484Q), His,Avitag™B.1.617

Preorder

Spike S1S1N-C52HtHis TagHEK293SARS-CoV-2 Spike S1 (T95I, G142D, E154K, L452R, E484Q, D614G, P681R), His TagB.1.617

Preorder

Spike S1S1N-C82E4His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 Spike S1 (T95I, G142D, E154K, L452R, E484Q, D614G, P681R), His,Avitag™B.1.617

Preorder

Spike proteinSPN-C52HrHis TagHEK293SARS-CoV-2 Spike Trimer (T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H), His TagB.1.617

Preorder

Spike proteinSPN-C82E7His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 Spike Trimer (T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H), His,Avitag™B.1.617

Preorder

Spike NTDS1D-C52HfHis TagHEK293SARS-CoV-2 Spike NTD (T95I, G142D, E154K), His TagB.1.617

Preorder

Nucleocapsid proteinNUN-C52HnHis TagHEK293SARS-CoV-2 Nucleocapsid protein (R203M, D377Y), His TagB.1.617

Preorder

MoleculeCat.No.TagHostProduct descriptionSpeciesPreorder/Order
S proteinSPN-C52H3His TagHEK293SARS-CoV-2 S protein (D614G), His Tag, Super stable trimer (MALS verified)B.1.1.7/B.1.351/P.1

Order

S proteinSPN-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein (D614G), His,Avitag™, Super stable trimer (MALS verified)B.1.1.7/B.1.351/P.1

Order

S proteinSPN-C52HkHis TagHEK293SARS-CoV-2 S protein (L18F, D80A, D215G, 242-244del, R246I, K417N, E484K, N501Y, D614G, A701V) trimer, His Tag (MALS verified)B.1.351

Order

S proteinSPN-C82E4His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein (L18F, D80A, D215G, 242-244del, R246I, K417N, E484K, N501Y, D614G, A701V) trimer, His,Avitag™ (MALS verified)B.1.351

Order

S1 proteinS1N-C5256His TagHEK293SARS-CoV-2 (COVID-19) S1 protein (D614G), His TagB.1.1.7/B.1.351/P.1

Order

S1 proteinS1N-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 (COVID-19) S1 protein (D614G), His,Avitag™B.1.1.7/B.1.351/P.1

Order

S1 proteinS1N-C52HmHis TagHEK293SARS-CoV-2 S1 protein (L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G), His TagB.1.351

Order

S1 proteinS1D-C5256Fc TagHEK293SARS-CoV-2 S1 protein (L18F, D80A, D215G, LAL242-244del, R246I, K417N, E484K, N501Y, D614G), Fc TagB.1.351

Order

S1 proteinS1N-C52HnHis TagHEK293SARS-CoV-2 S1 protein (E484K, D614G), His TagB.1.351/P.1

Order

S1 protein NTDS1D-C52HcHis TagHEK293SARS-CoV-2 S1 protein NTD (L18F, D80A, D215G, 242-244del, R246I), His Tag (MALS verified)B.1.351

Order

S protein RBDSPD-C52HsHis TagHEK293SARS-CoV-2 S protein RBD (K417N), His Tag (MALS verified)B.1.351

Order

S protein RBDSRD-C52H3His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (E484K), His Tag (MALS verified)B.1.351

Order

S protein RBDSPD-C52HpHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (K417N, E484K, N501Y), His Tag (MALS verified)B.1.351

Order

S protein RBDSPD-C5256Fc TagHEK293SARS-CoV-2 S protein RBD (K417N, E484K, N501Y), Fc Tag (MALS verified)B.1.351

Order

S protein RBDSPD-C82E5His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein RBD (K417N, E484K, N501Y), His,Avitag™B.1.351

Order

S2 proteinS2N-C52HcHis TagHEK293SARS-CoV-2 S2 protein (A701V), His TagB.1.351

Order

Nucleocapsid proteinNUN-C52HdHis TagHEK293SARS-CoV-2 Nucleocapsid protein (T205I), His TagB.1.351

Order

MoleculeCat.No.TagHostProduct descriptionSpeciesPreorder/Order
S proteinSPN-C52H3His TagHEK293SARS-CoV-2 S protein (D614G), His Tag, Super stable trimer (MALS verified)B.1.1.7/B.1.351/P.1

Order

S proteinSPN-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein (D614G), His,Avitag™, Super stable trimer (MALS verified)B.1.1.7/B.1.351/P.1

Order

S proteinSPN-C52H6His TagHEK293SARS-CoV-2 S protein (HV69-70del, Y144del, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H), His Tag (MALS verified)B.1.1.7

Order

S proteinSPN-C82E5His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein (HV69-70del, Y144del, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H) trimer, His,Avitag™ (MALS verified)B.1.1.7

Order

S1 proteinS1N-C52HdHis TagHEK293SARS-CoV-2 (COVID-19) S1 protein (HV69-70del), His TagB.1.1.7

Order

S1 proteinS1N-C52HcHis TagHEK293SARS-CoV-2 (COVID-19) S1 protein (Y144del), His TagB.1.1.7

Order

S1 proteinS1N-C52HbHis TagHEK293SARS-CoV-2 (COVID-19) S1 protein (P681H), His TagB.1.1.7

Order

S1 proteinS1N-C52HkHis TagHEK293SARS-CoV-2 (COVID-19) S1 protein (HV69-70del, N501Y, D614G), His TagB.1.1.7

Order

S1 proteinS1N-C52HrHis TagHEK293SARS-CoV-2 S1 protein (HV69-70del, Y144del, N501Y, A570D, D614G, P681H), His TagB.1.1.7

Order

S1 proteinS1N-C52HgHis TagHEK293SARS-CoV-2 (COVID-19) S1 protein (N501Y), His TagB.1.1.7/B.1.351

Order

S1 proteinS1N-C52H9His TagHEK293SARS-CoV-2 (COVID-19) S1 protein (A570D), His TagB.1.1.7

Order

S1 proteinS1N-C5256His TagHEK293SARS-CoV-2 (COVID-19) S1 protein (D614G), His TagB.1.1.7/B.1.351/P.1

Order

S1 proteinS1N-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 (COVID-19) S1 protein (D614G), His,Avitag™B.1.1.7/B.1.351/P.1

Order

S1 proteinS1D-C5254Fc TagHEK293SARS-CoV-2 S1 protein (HV69-70del, Y144del, N501Y, A570D, D614G, P681H), Fc TagB.1.1.7

Order

S1 protein NTDS1D-C52HdHis TagHEK293SARS-CoV-2 S1 protein NTD (HV69-70del, Y144del), His Tag (MALS verified)B.1.1.7

Order

S protein RBDSPD-C82E6His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein RBD (N501Y), His,Avitag™ (MALS verified)B.1.1.7

Order

S protein RBDSPD-C52HnHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (N501Y), His Tag (MALS verified)B.1.1.7/B.1.351

Order

S protein RBDSPD-C5253Fc TagHEK293SARS-CoV-2 S protein RBD (N501Y), Fc Tag (MALS verified)B.1.1.7

Order

S2 proteinS2N-C52HdHis TagHEK293SARS-CoV-2 S2 protein (T716I, S982A, D1118H), His TagB.1.1.7

Order

Nucleocapsid proteinNUN-C52H8His TagHEK293SARS-CoV-2 Nucleocapsid protein (D3L, R203K, G204R, S235F), His TagB.1.1.7

Order

MoleculeCat.No.TagHostProduct descriptionSpeciesPreorder/Order
S proteinSPN-C52H3His TagHEK293SARS-CoV-2 S protein (D614G), His Tag, Super stable trimer (MALS verified)B.1.1.7/B.1.351/P.1

Order

S proteinSPN-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein (D614G), His,Avitag™, Super stable trimer (MALS verified)B.1.1.7/B.1.351/P.1

Order

S proteinSPN-C52HgHis TagHEK293SARS-CoV-2 S protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F), His Tag (MALS verified)P.1

Order

S proteinSPN-C82E6His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F) trimer, His,Avitag™ (MALS verified)P.1

Order

S1 proteinS1N-C5256His TagHEK293SARS-CoV-2 (COVID-19) S1 protein (D614G), His TagB.1.1.7/B.1.351/P.1

Order

S1 proteinS1N-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 (COVID-19) S1 protein (D614G), His,Avitag™B.1.1.7/B.1.351/P.1

Order

S1 proteinS1D-C5253Fc TagHEK293SARS-CoV-2 S1 protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y), Fc TagP.1

Order

S1 proteinS1N-C52HpHis TagHEK293SARS-CoV-2 S1 protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y), His TagP.1

Order

S1 protein NTDS1D-C52HeHis TagHEK293SARS-CoV-2 S1 protein NTD (L18F, T20N, P26S, D138Y, R190S), His Tag (MALS verified)P.1

Order

S protein RBDSPD-C52HtHis TagHEK293SARS-CoV-2 S protein RBD (K417T), His Tag (MALS verified)P.1

Order

S protein RBDSPD-C52HrHis TagHEK293SARS-CoV-2 S protein RBD (K417T, E484K, N501Y), His Tag (MALS verified)P.1

Order

S protein RBDSPD-C82E7His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein RBD (K417T, E484K, N501Y), His,Avitag™P.1

Order

S protein RBDSPD-C5258Fc TagHEK293SARS-CoV-2 S protein RBD (K417T, E484K, N501Y), Fc Tag (MALS verified)P.1

Order

S2 proteinS2N-C52HeHis TagHEK293SARS-CoV-2 S2 protein (T1027I, V1176F), His TagP.1

Order

MoleculeCat.No.TagHostProduct descriptionSpeciesPreorder/Order
S1 proteinS1N-C52HsHis TagHEK293SARS-CoV-2 S1 protein (W152C, L452R, D614G), His TagB.1.427/B.1.429

Preorder

S protein RBDSPD-C52HeHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (L452R), His TagB.1.427/B.1.429

Order

Spike RBDSPD-C82E3His Tag & Avi TagHEK293Biotinylated SARS-CoV-2 S protein RBD (L452R), His,Avitag™B.1.427/B.1.429

Order

MoleculeCat.No.TagHostProduct descriptionSpeciesPreorder/Order
Nucleocapsid proteinNUN-C52HmHis TagHEK293SARS-CoV-2 Nucleocapsid protein (P13L), His Tag

Preorder

Nucleocapsid proteinNUN-C52HcHis TagHEK293SARS-CoV-2 Nucleocapsid protein (P80R), His TagP.1

Preorder

Nucleocapsid proteinNUN-C52H5His TagHEK293SARS-CoV-2 Nucleocapsid protein (D103Y), His Tag

Preorder

Nucleocapsid proteinNUN-C52HeHis TagHEK293SARS-CoV-2 Nucleocapsid protein (S194L), His Tag

Preorder

Nucleocapsid proteinNUN-C52H6His TagHEK293SARS-CoV-2 Nucleocapsid protein (S197L), His Tag

Preorder

Nucleocapsid proteinNUN-C52H3His TagHEK293SARS-CoV-2 Nucleocapsid protein (S202N), His Tag

Order

Nucleocapsid proteinNUN-C52H9His TagHEK293SARS-CoV-2 Nucleocapsid protein (L230F), His Tag

Order

Nucleocapsid proteinNUN-C52HfHis TagHEK293SARS-CoV-2 Nucleocapsid protein (I292T), His Tag

Order

Nucleocapsid proteinNUN-C52H4His TagHEK293SARS-CoV-2 Nucleocapsid protein (Q384H), His Tag

Order

Nucleocapsid proteinNUN-C52HgHis TagHEK293SARS-CoV-2 Nucleocapsid protein (R203K, G204R), His Tag

Order

S proteinSPN-C52HdHis TagHEK293SARS-CoV-2 S protein (F817P, A892P, A899P, A942P, K986P, V987P), His Tag (MALS verified)

Order

S1 protein NTDS1D-C52H8His TagHEK293SARS-CoV-2 (COVID-19) S1 protein NTD (A222V), His Tag (MALS verified)

Order

S1 protein NTDS1D-C52H7His TagHEK293SARS-CoV-2 (COVID-19) S1 protein NTD (N234Q), His Tag

Order

S1 protein NTDS1D-C52H5His TagHEK293SARS-CoV-2 S1 protein NTD (A262S), His Tag (MALS verified)

Order

S1 protein NTDS1D-C52H4His TagHEK293SARS-CoV-2 S1 protein NTD (P272L), His Tag (MALS verified)

Order

S protein RBDSPD-S52H5His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (N354D), His Tag

Order

S protein RBDSPD-S52H4His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (V367F), His Tag

Order

S protein RBDSPD-S52H8His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (R408I), His Tag

Order

S protein RBDSPD-S52H7His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (W436R), His Tag

Order

S protein RBDSPD-C52HgHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (N439K), His Tag (MALS verified)

Order

S protein RBDSRD-C52H2His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (N440K), His Tag (MALS verified)

Order

S protein RBDSPD-C52HkHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (Y453F), His Tag (MALS verified)

Order

S protein RBDSPD-C52HdHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (A475V), His Tag

Order

S protein RBDSPD-C52H4His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (G476S), His Tag

Order

S protein RBDSPD-C52HmHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (S477N), His Tag (MALS verified)

Order

S protein RBDSPD-C52H5His TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (V483A), His Tag

Order

S protein RBDSPD-C52HfHis TagHEK293SARS-CoV-2 (COVID-19) S protein RBD (F490L), His Tag

Order

S1 proteinS1N-C52HfHis TagHEK293SARS-CoV-2 (COVID-19) S1 protein (E583D), His Tag

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>>> If you have any customized inquiries or suggestions for new mutants, please click here.

 

Reference:

1.Nextstrain / ncov / global

2. Cherian, S., Potdar, V., Jadhav, S., et al. Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India. bioRxiv 2021.04.22.440932; doi: https://doi.org/10.1101/2021.04.22.440932

3. Hoffmann, M., Hofmann-Winkler, H., Krüger, N., et al. SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination. bioRxiv 2021.05.04.442663; doi: https://doi.org/10.1101/2021.05.04.442663

4. Kumar, V., Singh, J., Hasnain, S. E., Sundar, D. Possible link between higher transmissibility of B.1.617 and B.1.1.7 variants of SARS-CoV-2 and increased structural stability of its spike protein and hACE2 affinity. bioRxiv 2021.04.29.441933; doi: https://doi.org/10.1101/2021.04.29.441933

5. Ranjan, P., Neha, Devi, C., Das, P., et al. Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding. bioRxiv 2021.04.03.438113; doi: https://doi.org/10.1101/2021.04.03.438113

6. Yadav, P. D., Sapkal, G. N., Abraham, P., et al. Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. bioRxiv 2021.04.23.441101; doi: https://doi.org/10.1101/2021.04.23.441101

Latest Research on SARS-CoV-2 Variants

>>> Tracking of Variants from GISAID

  • SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

    Markus Hoffmann, Heike Hofmann-Winkler, Nadine Krüger, et.al

    doi: https://doi.org/10.1101/2021.05.04.442663

    Abstract: The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

  • Possible link between higher transmissibility of B.1.617 and B.1.1.7 variants of SARS-CoV-2 and increased structural stability of its spike protein and hACE2 affinity

    Vipul Kumar1, Jasdeep Singh, Seyed E. Hasnain, Durai Sundar

    doi: https://doi.org/10.1101/2021.04.29.441933

    Abstract: The Severe Acute syndrome corona Virus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has caused alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests, which also might lead to inefficacy of the available drugs. It has also increased the chances of reinfection and immune escape. We have performed Molecular Dynamic simulations of three different Spike-ACE2 complexes, namely Wildtype (WT), B.1.1.7 variant (N501Y Spike mutant) and B.1.617 variant (L452R, E484Q Spike mutant) and compared their dynamics, binding energy and molecular interactions. Our result shows that mutation has caused the increase in the binding energy between the Spike and hACE2. In the case of B.1.617 variant, the mutations at L452R and E484Q increased the stability and intra-chain interactions in the Spike protein, which may change the interaction ability of human antibodies to this Spike variant. Further, we found that the B.1.1.7 variant had increased hydrogen interaction with LYS353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2.

  • Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees

    Pragya D. Yadav, Gajanan N. Sapkal, Priya Abraham, M.D

    doi: https://doi.org/10.1101/2021.04.23.441101

    Abstract: The drastic rise in the number of cases in Maharashtra, India has created a matter of concern for public health experts. Twelve isolates of VUI lineage B.1.617 were propagated in VeroCCL81 cells and characterized. Convalescent sera of the COVID-19 cases and recipients of BBV152 (Covaxin) were able to neutralize VUI B.1.617.

  • Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India

    Sarah Cherian, Varsha Potdar, Santosh Jadhav, et al.

    doi: https://doi.org/10.1101/2021.04.22.440932

    Abstract: As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify   possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to selected monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation is warranted for accessing both ACE2 binding and the effectiveness of commonly elicited neutralizing mAbs for the strains of lineage B.1.617. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.

  • Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding

    Prashant Ranjan, Neha, Chandra Devi1and Parimal Das

    doi: https://doi.org/10.1101/2021.04.03.438113

    Abstract: Prevailing COVID-19 vaccines are based on the spike protein of earlier SARS-CoV-2 strain that emerged in Wuhan, China. Continuously evolving nature of SARS-CoV-2 resulting emergence of new variant/s raise the risk of immune absconds. Several RBD (receptor-binding domain) variants have been reported to affect the vaccine efficacy considerably. In the present study, we performed in silico structural analysis of spike protein of double mutant (L452R & E484Q), a new variant of SARS-CoV-2 recently reported in India along with K417G variants and earlier reported RBD variants and found structural changes in RBD region after comparing with the wild type. Comparison of the binding affinity of the double mutant and earlier reported RBD variant for ACE2 (angiotensin 2 altered enzymes) receptor and CR3022 antibody with the wildtype strain revealed the lowest binding affinity of the double mutant for CR3022 among all other variants. These findings suggest that the newly emerged double mutant could significantly reduce the impact of the current vaccine which threatens the protective efficacy of current vaccine therapy.

  • Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

    Pengfei Wang, Manoj S. Nair, Lihong Liu et al

    doi: https://doi.org/10.1101/2021.01.25.428137

    Abstract: The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody(mAb) therapeutics have received emergency use authorization, with more in the pipeline. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

  • SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

    Constantinos Kurt Wibmer, Frances Ayres, Tandile Hermanus et al

    doi: https://doi.org/10.1101/2021.01.18.427166

    Abstract: SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.

  • Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies

    Allison J. Greaney, Andrea N. Loes, Katharine H.D. Crawford et al

    doi: https://doi.org/10.1101/2020.12.31.425021

    Abstract: The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent serum antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of serum neutralizing activity. Binding by polyclonal serum antibodies is affected by mutations in three main epitopes in the RBD, but there is substantial variation in the impact of mutations both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor binding motif. The most important site is E484, where neutralization by some sera is reduced >10-fold by several mutations, including one in emerging viral lineages in South Africa and Brazil. Going forward, these serum escape maps can inform surveillance of SARS-CoV-2 evolution.

  • Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data

    Volz, Mishra*, Chand et al

    doi: https://doi.org/10.1101/2020.12.30.20249034

    Abstract: The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.

  • Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England

    Davies, Barnard, Jarvis et al

    doi: https://doi.org/10.1101/2020.12.24.20248822

    Abstract: A novel SARS-CoV-2 variant, VOC 202012/01, emerged in southeast England in November 2020 and appears to be rapidly spreading towards fixation. We fitted a two-strain mathematical model of SARS-CoV-2 transmission to observed COVID-19 hospital admissions, hospital and ICU bed occupancy, and deaths; SARS-CoV-2 PCR prevalence and seroprevalence; and the relative frequency of VOC 202012/01 in the three most heavily affected NHS England regions (South East, East of England, and London). We estimate that VOC 202012/01 is 56% more transmissible (95% credible interval across three regions 50-74%) than preexisting variants of SARS-CoV-2. We were unable to find clear evidence that VOC 202012/01 results in greater or lesser severity of disease than preexisting variants. Nevertheless, the increase in transmissibility is likely to lead to a large increase in incidence, with COVID-19 hospitalisations and deaths projected to reach higher levels in 2021 than were observed in 2020, even if regional tiered restrictions implemented before 19 December are maintained. Our estimates suggest that control measures of a similar stringency to the national lockdown implemented in England in November 2020 are unlikely to reduce the effective reproduction number Rt to less than 1, unless primary schools, secondary schools, and universities are also closed. We project that large resurgences of the virus are likely to occur following easing of control measures. It may be necessary to greatly accelerate vaccine roll-out to have an appreciable impact in suppressing the resulting disease burden.

  • Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

    Leung, Shum, Leung et al

    doi: https://doi.org/10.1101/2020.12.20.20248581

    Abstract: Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor binding domain of the spike protein have rapidly become prevalent in the UK. We estimated that the earlier 501Y lineage without amino acid deletion Δ69/Δ70 circulating mainly between early September to mid-November was 10% (6-13%) more transmissible than the 501N lineage, and the currently dominant 501Y lineage with amino acid deletion Δ69/Δ70 circulating since late September was 75% (70-80%) more transmissible than the 501N lineage.

  • Mutation Landscape of SARS-CoV-2 in Africa

    Nassir, Musanabaganwa, Mwikarago

    doi: https://doi.org/10.1101/2020.12.20.423630

    Abstract: COVID-19 disease has had a relatively less severe impact in Africa. To understand the role of SARS CoV2 mutations on COVID-19 disease in Africa, we analysed 282 complete nucleotide sequences from African isolates deposited in the NCBI Virus Database. Sequences were aligned against the prototype Wuhan sequence (GenBank accession: NC_045512.2) in BWA v. 0.7.17. SAM and BAM files were created, sorted and indexed in SAMtools v. 1.10 and marked for duplicates using Picard v. 2.23.4. Variants were called with mpileup in BCFtools v. 1.11. Phylograms were created using Mr. Bayes v 3.2.6. A total of 2,349 single nucleotide polymorphism (SNP) profiles across 294 sites were identified. Clades associated with severe disease in the United States, France, Italy, and Brazil had low frequencies in Africa (L84S=2.5%, L3606F=1.4%, L3606F/V378I/=0.35, G251V=2%). Sub Saharan Africa (SSA) accounted for only 3% of P323L and 4% of Q57H mutations in Africa. Comparatively low infections in SSA were attributed to the low frequency of the D614G clade in earlier samples (25% vs 67% global). Higher disease burden occurred in countries with higher D614G frequencies (Egypt=98%, Morocco=90%, Tunisia=52%, South Africa) with D614G as the first confirmed case. V367F, D364Y, V483A and G476S mutations associated with efficient ACE2 receptor binding and severe disease were not observed in Africa. 95% of all RdRp mutations were deaminations leading to CpG depletion and possible attenuation of virulence. More genomic and experimental studies are needed to increase our understanding of the temporal evolution of the virus in Africa, clarify our findings, and reveal hot spots that may undermine successful therapeutic and vaccine interventions.

  • Major new lineages of SARS-CoV-2 emerge and spread in South Africa during lockdown

    Tegally, Wilkinson, Lessells et al

    doi: https://www.medrxiv.org/content/10.1101/2020.10.28.20221143v1

    Abstract: In March 2020, the first cases of COVID-19 were reported in South Africa. The epidemic spread very fast despite an early and extreme lockdown and infected over 600,000 people, by far the highest number of infections in an African country. To rapidly understand the spread of SARS-CoV-2 in South Africa, we formed the Network for Genomics Surveillance in South Africa (NGS-SA). Here, we analyze 1,365 high quality whole genomes and identify 16 new lineages of SARS-CoV-2. Most of these unique lineages have mutations that are found hardly anywhere else in the world. We also show that three lineages spread widely in South Africa and contributed to ∼42% of all of the infections in the country. This included the first identified C lineage of SARS-CoV-2, C.1, which has 16 mutations as compared with the original Wuhan sequence. C.1 was the most geographically widespread lineage in South Africa, causing infections in multiple provinces and in all of the eleven districts in KwaZulu-Natal (KZN), the most sampled province. Interestingly, the first South-African specific lineage, B.1.106, which was identified in April 2020, became extinct after nosocomial outbreaks were controlled. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify and control the spread of SARS-CoV-2.

  • Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa

    Tegally, Wilkinson, Giovanetti et al

    doi: https://doi.org/10.1101/2020.12.21.20248640

    Summary: Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

  • Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report

    Giandharia, Pillaya, Wilkinson et al

    Int J Infect Dis(2020)11, 128

    doi: https://doi.org/10.1016/j.ijid.2020.11.128

    Abstract: Objectives: The Network for Genomic Surveillance in South Africa (NGS-SA) was formed to investigate the introduction and understand the early transmission dynamics of the SARS-CoV-2 epidemic in South-Africa.
                               Design: This paper presents the first results from this group, which is a molecular epidemiological study of the first 21 SARS-CoV-2 whole genomes sampled in the first port of entry – KwaZulu-Natal (KZN) –during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), it aimed to shed light on the patterns of infections in South Africa.
                               Results: Two of the largest provinces – Gauteng and KZN – had a slow growth rate for the number of detected cases, while the epidemic spread faster in the Western Cape and Eastern Cape. The estimates of transmission potential suggested a decrease towards R = 1 since the first cases and deaths, but a subsequent estimated R average of 1.39 between 6–18 May 2020. It was also demonstrated that early transmission in KZN was associated with multiple international introductions and dominated by lineages B1 and B. Evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic was also provided.
                               Conclusion: The COVID-19 pandemic in South Africa was very heterogeneous in its spatial dimension, with many distinct introductions of SARS-CoV2 in KZN and evidence of nosocomial transmission, which inflated early mortality in KZN. The epidemic at the local level was still developing and NGS-SA aimed to clarify the dynamics in South Africa and devise the most effective measures as the outbreak evolved.

  • Brief report: New Variant Strain of SARS-CoV-2 Identified in Travelers from Brazil

    January 12, 2021

    National Institute of Infectious Diseases, JAPAN

    Technical detail: The variant isolate (GISAID ID: EPI_ISL_792680 to 792683) belongs to B.1.1.248 lineage and has 12 mutations in the spike protein, including N501Y and E484K. - N501Y is a mutation found in variant strains including VOC-202012/01 and 501Y.V2, implicated to increase transmissibility. - The E484K was reported to be an escape mutation from a monoclonal antibody which neutralize SARSCoV-2 (1,2). The E484K has been observed in variant isolates escaping from convalescent plasma (3) and with a 10-fold decrease in neutralization capability by convalescent plasma (4)(both in preprint articles), suggesting possible change in antigenicity. - In Brazil, a variant isolate with E484K belonging to B.1.1.248 was reported on January 6, 2021 (5), but it is not identical to the new variant isolate identified in Japan.

  • Researchers Discover New Variant of COVID-19 Virus in Columbus, Ohio

    January 13, 2021

    The Ohio State University Wexner Medical Center

    Scientists at The Ohio State University Wexner Medical Center and College of Medicine have discovered a new variant of SARS-Cov-2, the virus that causes COVID-19. The new variant carries a mutation identical to the U.K. strain, but it likely arose in a virus strain already present in the United States. The researchers also report the evolution of another U.S. strain that acquired three other gene mutations not previously seen together in SARS-CoV2.

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