Decoding the lethal effect ofSARS-CoV-2(novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence

Abstract

Background COVID-19 is a disease with global public health emergency that have shook the world since its' first detection in China in December, 2019. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible behind this pandemic. The lethality of different viral strains is found to vary in different geographical locations but the molecular mechanism is yet to be known.Methods Available data of whole genome sequencing of different viral strains published by different countries were retrieved and then analysed using Multiple Sequence Alignment and Pair-wise Sequence Alignment leading to Phylogenetic tree construction. Each location and the corresponding genetic variations were screened in depth. Then the variations are analysed at protein level giving special emphasis on Non Synonymous amino acid substitutions. The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination. FindingsAll the viral strains have been found to evolve from the viral strain of Taiwan (MT192759) which is 100% identical with the ancestor SARS-CoV-2 sequences of Wuhan (NC 045512.2; submitted on 5 th Jan, 2020). Transition from C to T (C>T) is the most frequent mutation in this viral genome and mutations A>T, G>A, T>A are the rarest ones, found in countries with maximum fatality rate i.e Italy, Spain and Sweden. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. The functional effect on the structure and function of the protein can favourably or unfavourably interact with the host body.

Mutational spectra of SARS‐CoV‐2 orf1ab polyprotein and signature mutations in the United States of America

“…Nsp 6 plays a role in the initial induction of autophagosomes from the host endoplasmic reticulum, but gradually limits the expansion of these phagosomes which are unable to deliver viral components to lysosomes. It is important to note here that 3606 L→F mutations were found in Italy while analyzing Group C (present study), which further strengthens our previous reporting 10 …”

Geographical variation in case fatality rate and doubling time during the COVID-19 pandemic

“…There would be more mild cases that would be detected and hence the cCFR estimates would fall as these mild cases are more likely to recover. There is also limited evidence to suggest that different strains may be present in different countries having variations in cCFR between strains [13]. There is a need to focus on broader issues such as standardisation of definitions, testing strategies and reporting format across countries to make more plausible comparisons.…”

Changing Epidemiology of SARS-CoV in the Context of COVID-19 Pandemic

“…The mutation in the receptor binding domain and the polybasic furin cleavage site on the spike protein might be the major contributor of the significant infectivity and transmissibility to the virus. However, research indicated that different transition type of point mutation causes the virus heterogeneity in different geographical regions [20]. These ultimately affect the virus infectivity.…”