![]() These targets are a choice for inhibition purpose also in SARS-CoV and MERS-CoV, and hence, constant work has been carried out either by computational methods or experimental investigations to find novel molecules which can interfere with virus life cycle by inhibiting the main protease. Inhibiting the viral activity of this enzyme would block the replicase-transcriptase complex and therefore disrupt the viral life cycle. Ĭonsidering the functional significance of the main protease, i.e., to carry out processing of polyproteins into NSPs, in the viral life cycle, and combined with the absence of closely related homologues in humans, main protease serves as an attractive target for the design of antiviral drugs. There have been continuous research efforts to develop antiviral agents against members of Coronaviridae family which suggested that the human receptor, angiotensin-converting enzyme 2 that facilitates entry of virus into the host, RNA-dependent RNA polymerase and main protease, helicase, and papain-like protease, may be represented as suitable drug targets. Despite the availability of vaccines and large populations in various countries being already vaccinated, the re-emergence of SARS-CoV2 in the mutated forms as witnessed in the case of beta and omicron variants poses a continuous threat of COVID-19 disease. More than 530 million COVID-19 cases and close to 6.29 million deaths have been reported during the last 2 years and 5 months. It was also observed that patients with comorbidity pose a greater risk of developing severe infection which may also result in death of an individual. The condition could worsen due to respiratory failure leading to the death of the patient. The most prominent symptom reported in SARS-CoV2 is respiratory distress with some patients requiring intensive care, high-flow oxygen therapy, and invasive and noninvasive ventilation. A type-3 transmembrane glycoprotein also known as membrane protein and the envelope protein are situated among the spike proteins in the virus envelope. The virion contains a nucleocapsid made up of genomic RNA and phosphorylated nucleocapsid protein, buried inside the phospholipid bilayers and surrounded by spike protein on the membrane of virus. Various enzymes including the main protease also called as 3-chymotrypsin-like protease (NSP5), papain-like protease (NSP3), and RNA-dependent RNA polymerase (NSP12) are present in this complex among other proteins. These polyproteins are further processed into 16 nonstructural proteins (NSPs), NSP1 to NSP16, which constitute the replicase-transcriptase complex. The SARS-CoV2 genome encodes open-reading frames (ORFs) ORF1a and ORF1ab that encode for polyproteins. The RNA genome of the human SARS-CoV2 is 82% identical to that of human SARS-CoV and shares considerable similarity in the genome hence, it has been named as SARS-CoV2. These are nonsegmented, enveloped, positive‐sense single‐stranded RNA virus genomes, and the human coronaviruses have the genomic size ranging from 29 to 31 kilobases. ![]() All these viruses belong to the subfamily Coronavirinae in a family Coronaviridae. During the last 2 years, the novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) that causes coronavirus disease 2019 (COVID-19) resulting in an acute infection in the respiratory system, has become a global pandemic. ![]() The world previously witnessed outbreaks of coronavirus disease caused by other similar species, namely SARS-CoV in 20 in China MERS-CoV in 2012 in the Middle East HCoV-OC43 in 1967 in Salisbury, UK HCoV-229E in 1966 in African bats HCoV-HKU1 in 2005 in Hong Kong and HCoV-NL63 in 2002–2003 across Asia, Europe, and North America. Coronaviruses pose a continuous threat to the mankind because of their ability to emerge unpredictably and periodically, thereby spreading rapidly and inducing serious infectious pandemic disease. Coronaviruses comprise a large family of zoonotic viruses that have potential to infect humans via animal intermediaries. ![]()
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