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. Graphical abstract Schematic representation of novel corona virus showing target proteins and its mechanism of host entry. Unlabelled Image Highlights • 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.
【저자키워드】 COVID-19, SARS-CoV-2, COVID-19, Coronavirus disease 2019, ACE2, angiotensin-converting enzyme 2, molecular evolution, Comparative genomics, drug target, SARS-CoV, severe acute respiratory syndrome coronavirus, RBD, receptor binding domain, JAK, Janus kinase, NSP, nonstructural protein, IL, interleukin, UTR, untranslated region, WHO, World Health Organization, TNF, Tumor Necrosis Factor, FDA, Food and Drug Administration, ORF, open reading frame, TMPRSS2, Transmembrane Protease Serine 2, S, spike protein, MERS-CoV, Middle-East respiratory syndrome coronavirus, N, nucleocapsid protein, G-CSF, granulocyte-colony stimulating factor, IFNγ, Interferon, M, Membrane protein, E, Envelope protein, STAT, Signal transducer and activator of transcription protein, Molecular basis of pathogenesis,