Characterizing SARS-CoV-2 mutations in the United States

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, k-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations were first detected in China (2 cases), Singapore (2 cases), and the United Kingdom (1 case). The next three top US SARS-CoV-2 mutations were first detected in the US. These eight top mutations belong to two disconnected groups. The first group consisting of 5 concurrent mutations is prevailing, while the other group with three concurrent mutations gradually fades out. We identify that one of the top mutations, 27964C>T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we further uncover that three of four US SASR-CoV-2 substrains become more infectious. Our study calls for effective viral control and containing strategies in the US.

Mutational analysis of SARS-CoV-2 ORF8 during six months of COVID-19 pandemic

“…Mutations could be dynamic, as it has been proposed that some mutations like L84S are disappearing, and there is emergence of new ones that render the virus more infective, like S24L that was first sequenced in the USA ( Wang et al, 2020b ). This could explain the weak signal of population expansion whose distribution of S24L, on a large number of sequences, and, at the same time, of L84S increased the Pi value and added some equilibrium with the low frequency of new mutations.…”

“…SARS-CoV-2 ORF8 protein has been shown to be implicated in immune evasion by downregulating surface expression of MHC-1 ( Zhang et al, 2020 ). Wang and colleagues ( Wang et al, 2020b ) showed that L84S decreases the function of ORF8, and thus is beneficial for human immune system, whilst S24L increases its function since it reinforces protein folding stability. As for deletions, 382 nts deletion was shown to cause milder infection ( Young et al, 2020 ).…”

Change of dominant strain during dual SARS-CoV-2 infection

“…Spike_D614G is one of the most widely discussed mutations. Its presence defines G clade [25], it increases infectivity [32][33][34], mortality [35,36], alters viral fitness [37], and, according to protein modeling, strengthens the folding stability of the spike protein [28]. It is present in 99.2 % of SARS-CoV-2 genomes obtained from Russia (as of 11.11.2020).…”

<strong>V483a – an Emerging Mutation Hotspot of Sars-Cov-2</strong>

“…Positive binding affinity also indicates that the mutation will help in making tighter interaction with the receptor. 15 Cryo EM studies show that this type of nonsynonymous single nucleotide variations may affect the strength of transmission of the virus. 22 The dynamic studies on a structural basis due to this mutation revealed that the binding surface of the RBD to ACE2 is having largely random coil conformation and it is lacking structural rigidity.…”

“…The mutation occurrence from the month of March, 2020 till date is reported as 366 (FIG. 3)and thus this mutant is found to be more prevalent in the United States 15.…”