Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1866; no. 10; p. 165878
• Main Authors: Naqvi, Ahmad Abu Turab, Fatima, Kisa, Mohammad, Taj, Fatima, Urooj, Singh, Indrakant K., Singh, Archana, Atif, Shaikh Muhammad, Hariprasad, Gururao, Hasan, Gulam Mustafa, Hassan, Md. Imtaiyaz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020
• Subjects: Betacoronavirus - genetics; Betacoronavirus - isolation & purification; Betacoronavirus - pathogenicity; Comparative genomics; Coronavirus Infections - drug therapy; Coronavirus Infections - pathology; Coronavirus Infections - virology; COVID-19; Cytokines - metabolism; Drug target; Genetic Variation; Genome, Viral; Humans; Middle East Respiratory Syndrome Coronavirus - genetics; Middle East Respiratory Syndrome Coronavirus - isolation & purification; Middle East Respiratory Syndrome Coronavirus - pathogenicity; Molecular basis of pathogenesis; Molecular evolution; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; RNA-Dependent RNA Polymerase - genetics; SARS-CoV-2; Spike Glycoprotein, Coronavirus - chemistry; ORF; FDA; E; SARS-CoV; Molecular basis of pathogenesis; Comparative genomics; TMPRSS2; MERS-CoV; TNF; M; N; COVID-19; UTR; SARS-CoV-2; S; RBD; WHO; IFNγ; IL; Drug target; Nsp; G-CSF; ACE2; Molecular evolution; STAT; JAK
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2020.165878

The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective. Schematic representation of novel corona virus showing target proteins and its mechanism of host entry. [Display omitted] •The recent exposure to SARS-CoV-2 has affected entire world, resulted >0.4 million deaths.•Potential drug targets of SARS-CoV-2 are highly conserved.•A slight structural difference makes available drugs ineffective against SARS-CoV-2.•Cytokine storm during SARS-CoV-2 infection may be targeted to handle COVID-19 patients.•Many FDA approved drugs are showing positive effects in clinical trials but further validation in large subject groups is required.