Generalized linear models provide a measure of virulence for specific mutations in SARS-CoV-2 strains

Abstract

This study aims to highlight SARS-COV-2 mutations which are associated with increased or decreased viral virulence. We utilize genetic data from all strains available from GISAID and countries’ regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of specific mutations can be obtained from calculating their frequencies across viral strains. By applying modelling approaches, we provide additional information that is not evident from standard statistics or mutation frequencies alone. We therefore, propose a more precise way of selecting informative mutations. We highlight two interesting mutations found in genes N (P13L) and ORF3a (Q57H). The former appears to be significantly associated with decreased deaths and cases per million according to our models, while the latter shows an opposing association with decreased deaths and increased cases per million. Moreover, protein structure prediction tools show that the mutations infer conformational changes to the protein that significantly alter its structure when compared to the reference protein.

Emergence of the novel SARS-CoV-2 lineage VUI-NP13L and massive spread of P.2 in South Brazil

“…Since the ORF9b is involved in the suppression of IFN-I antiviral response [ 46 ], further investigation is necessary to evaluate the role of P10S mutation on this process. In respect to the N protein, the P13L mutation is related to lower mortality rates of SARS-CoV-2 [ 46 , 47 ].…”

In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches

“…Capitalizing on previously published generalized linear models (glms) that provide a measure of association between specific SARs-CoV-2 mutations and increased or decreased viral cases or deaths [10], we proceeded to perform virulence analysis on the 18 mutations found to be prevalent in the Cypriot population. We focused on the S6059F mutation due to its exclusive propagation within Cyprus compared to the rest of the world.…”

“…Applying our previously published glm model [10], on the 18 Cyprus-specific mutations allows for the analysis of these less studied mutations and how they appear to correlate with death and transmission rates. According to the fitting plot of our glm models, the unique S6059F mutation appears to be positively correlated with deaths per million (R=0.61) and neutral with respect to cases (R=0.15) per million (see supplementary Figure S2 ).…”

“…Furthermore, we identify Cypriot-specific/dominant mutations and investigate them using mutation tracking analysis in order to isolate their origin, determine their founder effect in Cyprus and also trace their overall prevalence and propagation in other countries. We capitalize on our previously published generalized linear models [10] to undertake virulence analysis on Cypriot-dominant mutations and show how their presence has affected the number of cases and deaths within the country. Finally, we perform structural modelling of the alternate versus the reference mutation for selected mutations of interest and view their effects at the viral protein level.…”

Demographic Analysis of Mutations in Indian SARS-CoV-2 Isolates

“…The mutation C28311T (N: P13L) is located in the protein's intrinsically disordered region and may impair the terminal domain's RNA-binding function [24,25]. A previous study evaluated how this mutation may alter protein-protein interaction and proposed its impact on virus stability, potentially contributing to lower pathogenesis [26]. From the protein stability analysis using I-Mutant2.0 and MUpro given in Table 1, the two non-synonymous mutations representing subclade I/A3i (C6312A and C13730T) decrease the stability.…”