Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure

Chand, Gyanendra Bahadur; Azad, Gajendra Kumar

doi:10.1101/2020.05.05.079939

Cited by 28 publications

(38 citation statements)

References 18 publications

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“…Alarmingly, P323L that is located in the proximity of NSP8 binding site (Figure 4, PDB ID: 6YYT) is found in 71 countries (except Brunei, Croatia, Iran, Malaysia, South Korea, Nepal, Philippines, Turkey, Pakistan, Tunisia, Guam and Uruguay) out of 84 countries considered here with a high significance (75% mutation rate in the second phase) (Figure 2). Prevalence of this mutation is also reported earlier 7,[33][34][35] . Next, A97V (England, India, Singapore and Australia taking the top 4 positions among the 14 countries) occurs at a moderate significance (1.6%) in the second phase (Figure 3).…”

Section: Pdb Id: 6zct 7bq7)supporting

confidence: 68%

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Patro

Sathyaseelan

Uttamrao

et al. 2020

Preprint

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To accelerate the drug and vaccine development against the severe acute respiratory syndrome virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F-NSP6, P323L-NSP12, D614G-spike, Q57H-ORF3a, G251V-ORF3a, L84S-ORF8, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring mutations and P323L-NSP12 and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85-NSP1 deletion, D268-NSP2 deletion, 112 amino acids deletion in ORF8, a phenylalanine insertion amidst F34-F36 (NSP6) and several co-existing substitution/deletion (I559V & P585S in NSP2, P504L & Y541C in NSP13, G82 & H83 deletions in NSP1 and K141, S142 & F143 deletions in NSP2) mutations. P323L-NSP12, D614G-spike, L37F-NSP6, L84S-ORF8 and the sequences deficient of the high significant mutations has led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations has evolved in the first phase and has already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid protein, ORF3a, ORF8, RNA dependent RNA polymerase and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9, NSP10, NSP8, the envelope protein and NSP4 are highly resistant to mutations and can be exploited for drug/vaccine development.

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Section: Pdb Id: 6zct 7bq7)supporting

confidence: 68%

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Patro

Sathyaseelan

Uttamrao

et al. 2020

Preprint

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“…The P4715L mutation (14408 C>T) in the viral polyprotein ORF1ab located in the RNA-dependent RNA polymerase region (position 323 of RdRP), which could be related to the increase in the mutation rate (14). This polymerase dynamics simulation indicates that this P4715L is a more stable RdRP variant (15). The spike protein´s D614G mutation is related to the increase of the virus´s infectivity and is present in 29 of the 35 genomes reported in Peru (16).…”

Section: Discussionmentioning

confidence: 86%

Genomic analysis reveals local transmission of SARS-CoV-2 in early pandemic phase in Peru

Padilla‐Rojas

Vega-Chozo

Galarza-Pérez

et al. 2020

Preprint

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The dissemination of cases of the new SAR-COV-2 coronavirus represents a serious public health problem for Latin America and Peru. For this reason, it is important to characterize the genome of the isolates that circulate in Latin America. To characterize the complete genome of first samples of the virus circulating in Peru, we amplified seven overlapping segments of the viral genome by RT-PCR and sequenced using Miseq platform. The results indicate that the genomes of the Peruvian SARS-COV-2 samples belong to the genetic groups G and S. Likewise, a phylogenetic and MST analysis of the isolates confirm the introduction of multiple isolates from Europe and Asia that, after border closing, were transmitted locally in the capital and same regions of the country. These Peruvian samples (56%) grouped into two clusters inside G clade and share B.1.1.1 lineage. The characterization of these isolates must be considered for the use and design of diagnostic tools, and effective treatment and vaccine formulations.

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“…5.E). Protein dynamics simulations showed an increase in stability of the Nsp12 P323L variant 25 . In absence of P322, the mutation P323L would probably be disfavored due to flexibilization of the turn in the end of helix 10.…”

Section: C14408tmentioning

confidence: 97%

Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases during the Pandemic

Arévalo

Sifuentes

Robles

et al. 2020

Preprint

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Since the identification of SARS-CoV-2 in December 2019 a large number of SARS-CoV-2 genomes has been sequenced with unprecedented speed around the world and deposited in several databases. This marks a unique opportunity to study how a virus spread and evolve in a worldwide context. However, currently there is not a useful haplotype classification system to help tracking the virus evolution. Here we identified eleven mutations with 10 % or more frequency in a data set of 7848 genomes. Using these mutations, we identified 6 SARS-CoV-2 haplotypes or OTUs (Operational Taxonomic Unit) that correlate well with a phylogenomic tree. After that, we analyzed the geographical and temporal distribution of these OTUs, as well as their correlation with patient status. Our geographical analysis showed different OTUs prevalence between continents and the temporal distribution analysis revealed an evolution-like pattern in SARS-CoV-2. Finally, we observed a homogenous distribution of OTUs in mild and severe patients and a great prevalence of OTU 2 in asymptomatic patients. However, genomes in the asymptomatic category, comes from isolates on three consecutive days in February (15 to 17), weakening this observation and highlighting the need to increase genomic analyzes in asymptomatic and severe patients. Our classification system is phylogenetically consistent and allows us to easily track geographic and temporal distribution of important mutations around the world. In the next months, it could be updated using similar steps that we used here.

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Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure

Cited by 28 publications

References 18 publications

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

Genomic analysis reveals local transmission of SARS-CoV-2 in early pandemic phase in Peru

Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases during the Pandemic

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