Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment

Abstract

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat COVID-19. Several approaches are being used by scientists for investigation, including (1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease; and (2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries, such as the Netherlands, Switzerland, and France, but seldom observed in China.

Variant analysis of SARS-CoV-2 genomes

“…The most common clade identified was the D614G variant, which is located in a B-cell epitope with a highly immunodominant region and may therefore affect vaccine effectiveness. 33 Although amino acids are quite conserved in this epitope, we identified S359N D364Y V367F K378R F338L V341I A348T W353R P384L P330S V289I E309Q L296H E298G V308L G476S V483A/I N439K S438F A520S T547I P561L A570T/V A575S G594S R408* Q409E I434K A435S K458R/N D467V I468F/T C432* I472V P491R Y508H H519P/Q Q414A/E K417* G446V L452R A475V T478I V503F R509K V510L K529E E554D T573I T572I E583D L585F D405V D614G V615F/L T630S L611F V622I/L P631S A626V D627H N603K Q613H P621S D808N P809S P812S/L F817L I818V G889S A892S A893V Q804K I805V N354D/K S359N D364Y V367F K378R F338L V341I A348T W353R P384L P330S G476S V483A/I N439K S438F A520S R408* Q409E I434K A435S K458R/N D467V I468F/T D467V 6 C432* I472V P491R Y508H H519P/Q A520S Q414A/E K417* G446V L452R A475V T478I V503F R509K V510L D405V V289I E309Q L296H E298G V308L G594S D614G V615F/L D614G D614G T630S L611F V622I/L P631S A626V D627H N603K Q613H D614G D614G P621S D808N P809S P812S/L F817L I818V Q804K I805V Q Q G889S A892S A893V T547I P561L A570T/V A575S K529E E554D T573I T572I E583D L585F RBD: receptor binding domain B-cell epitope (predicted) SARS-CoV-2: severe acute respiratory syndrome coronavirus 2. Notes: We al...…”

coronapp: A Web Application to Annotate and Monitor SARS-CoV-2 Mutations

“…To date, much effort has been made to develop therapeutic strategies to limit SARS-CoV-2 transmission and replication, but no treatment or vaccine has proven effective against the virus, and repurposing of approved therapeutic agents has been the main practical approach to manage the emergency so far [7]. As viruses mutate during replication, the emergence of SARS-CoV-2 sub-strains and the challenge of a probable antigenic drift require attention, especially for vaccine development [8].…”

Infectivity of SARS-CoV-2: there Is Something More than D614G?

“…As anticipated, SARS-CoV-2 evolution is most likely through selection, perhaps conferring enhanced fitness and/or infectivity. Numerous reports detail the molecular identification of D614G mutation in Spike protein (S-protein) (Korber et al 2020;Koyama et al 2020;Maitra et al 2020) and are experimentally characterizing the functional impact upon the viral life cycle (Li et al 2020;Luthy and Kistler 1989). Regardless of how D614G arose, it is clear that this variant has a distinct phenotype.…”