ABSTRACT
Viral outbreaks had been a threat for the human race for a long time. Several epidemics and pandemics have been reported in the past with serious consequences on human health and subsequent social and economic aspects. According to WHO, viral infections continue to be a major health concern globally. Novel coronavirus, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) causes the most recent infectious pandemic disease, COVID-19 (Coronavirus disease-19). As of now, there were 249 million infections of COVID-19 worldwide with a high mortality of more than 5 million deaths reported; and the number of new additional cases is drastically increasing. Development of therapies to treat the infected cases and prophylactic agents including vaccines that are effective towards different variants are crucial to curtail the COVID-19 pandemic. Owing to the fact that there is a high mortality and morbidity rate along with the risk of virus causing further epidemic outbursts, development of additional effective therapeutic and preventive strategies are highly warranted. Prevention, early detection and treatment will reduce the spread of COVID-19 pandemic. The present review highlights the novel mutations and therapeutic updates associated with coronaviruses along with the clinical manifestations-diagnosis, clinical management and, prophylactic and therapeutic strategies of COVID-19 infection.
Subject(s)
COVID-19 , Vaccines , Humans , Mutation , Pandemics , SARS-CoV-2ABSTRACT
The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is spreading, as the causative pathogen of coronavirus disease-19 (COVID-19). It has infected more than 1.65 billion people all over the world since it was discovered and reported 3.43 million deaths by mid of May 2021. SARS-CoV-2 enters the host cell by binding to viral surface glycoprotein (S protein) with human ACE2 (angiotensin-converting enzyme2). Spike protein (contains S1 and S2 sub-domains) molecular interaction with the host cells is considered as a major step in the viral entry and disease initiation and progression and this identifies spike protein as a promising therapeutic target against antiviral drugs. Currently, there are no efficient antiviral drugs for the prevention of COVID-19 infection. In this study, we have analyzed global 8719 spike protein sequences from patients infected with SAR-CoV-2. These SAR-CoV-2 genome sequences were downloaded from the GISAID database. By using an open reading frame (ORF) tool we have identified the spike protein sequence. With these, all spike protein amino acid sequences are subjected to multiple sequence alignment (MSA) with Wuhan strain spike protein sequence as a query sequence, and it shows all SAR-CoV strain spike proteins are 99.8% identical. In the mutational analysis, we found 639 mutations in the spike protein sequence of SARS-CoV-2 and identified/highlighted 20 common mutations L5F, T22I, T29I, H49Y, L54F, V90F, S98F, S221L, S254F, V367F, A520S, T572I, D614G, H655Y, P809S, A879S, D936Y, A1020S, A1078S, and H1101Y. Further, we have analyzed the crystal structure of the 2019-nCoV chimeric receptor-binding complex with ACE2 (PDB ID: 6VW1) as a major target protein. The spike receptor binding protein (RBD) used as target region for our studies with FDA-approved drugs for repurposing, and identified few anti-SARS-CoV2 potential drugs (Silmitasertib, AC-55541, Merimepodib, XL413, AZ3451) based on their docking score and binding mode calculations expected to strongly bind to motifs of ACE2 receptor and may show impart relief in COVID-19 patients.