The toughest situations of the era are currently being faced internationally, with lot of regulations rapidly evolved and changed our way of life in an unprecedented manner to stop the spread of the virus, COVID–19. The Wuhan city of Hubei province in China became the first victim of the virus attack. The World Health Organization (WHO) on January 12, 2020 temporarily named this virus as 2019 novel coronavirus (2019-nCoV) and one month later, WHO renamed it as SARS CoV–2 (Severe acute respiratory syndrome coronavirus–2) as it showed 89.1% nucleotide similarity with SARS CoV (Wu, Zhao, et al.,, 2020). Coronaviruses infect different species including mammals and aves and can cause chronic diseases that affect the respiratory, neurological and gastrointestinal systems (Bosch et al.,, 2003). SARS CoV unfolded to five continents within the year 2003 with a death rate of 10%, affecting almost 8000 people and about 800 death for which the host was identified to be bat (Cheng et al.,, 2007). Later in 2012, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) broke out in the regions of Arabian Peninsula with a lethal rate of 35% and the host was dromedary (Wu, Liu, et al.,, 2020). The first whole genomic sequence of SARS CoV–2 was published by Zhang and his team (Wu, Zhao, et al.,, 2020). SARS CoV–2 belongs to the beta-coronavirus group, sharing its ancestry with the HKU9–1 (Xu et al.,, 2020; Coutard et al.,, 2020) bat coronavirus, homologous to SARS CoV. On January 30, WHO declared a Public Health Emergency of International Concern (PHEIC) as it commenced to take the lives of many humans without any precise approved remedy and its quick unfold to many countries worldwide due to human-to-human transmission. COVID–19 has been declared as a pandemic by the WHO on March 11. As of 29th April 2020, the number of confirmed cases are almost 3 million in 213 countries with more than 2,00,000 deaths and the rates are still mounting.
The enveloped coronaviruses belong to genus of the coronaviridae family and subfamily coronavirine and possess a genome with the longest single stranded positive sense RNA of 27–32 kb (van der Hoek, 2004). The virus that infects the host cells act similar to a messenger RNA that helps in the synthesis of various kinds of proteins which includes the ones that help in their replication. The genome of SARS CoV–2 is identical to other beta-coronaviruses in many ways like the 5’-untranslated region (UTR), a replicase complex (orf1ab) which encodes the non-structural proteins, few structural proteins, 3’-UTR and some unidentified non-structural open reading frames (Zhu et al.,, 2020). The non-structural proteins involve main protease (Mpro), papain-like protease (PLpro), non-structural protein–12 (nsp–12), nsp–13, nsp–14, nsp–15, nsp–16, and nsp–10. The sub-genomic RNA’s are translated into the structural proteins like the spike protein (S protein) containing the receptor binding domain (RBD) which invades the host cell through the cell surface receptor, angiotensin-converting enzyme 2 (ACE–2). The viral fusion protein (S2 of S protein) assists in membrane fusion of virus with the host cells. Further, envelop small membrane protein (E protein) functions as ion channel, membrane protein (M protein) involves in protein-protein interaction that is required for the assembly of coronaviruses and nucleocapsid protein (N protein) play multiple roles in viral replication cycle like modulating the host cell, regulating viral RNA synthesis. The binding of the spike protein with the cell membrane is initiated by enzymes like trypsin, furin, cathepsin L (Hasan et al.,, 2020).
The common symptoms that accompany with the disease are fever, cough, headache, shortness of breath, dyspnea, whereas some acute cases will have pneumonia, kidney failure and even death due to the infection. Differentiation of SARS CoV–2 from the most common symptoms of atypical pneumonia and etiological diagnosis is possible only through laboratory tests. WHO recommended for the screening of the suspected samples with nucleic acid amplification tests (NAAT) like real-time reverse-transcription polymerase chain reaction (rRT-PCR) of the upper respiratory specimens (like nasopharyngeal and oropharyngeal swab) for patients under observation. Patients with severe symptoms are to be tested with the lower respiratory specimens like sputum or endotracheal aspirate (WHO, Interim guidance, 2020). WHO also advised the detection of antigen in the respiratory samples to confirm the presence of viral proteins expressed by SARS CoV–2. This test is used to detect early or at the severe stages of infection as the concentration of serum antibody rises after few days of the infection. Another detection method is based on the host antibody detection which detects the presence of antibodies in the blood samples of people suspected of COVID–19. But this test does not work in the early stage of the infection as the antibodies will develop only after few days or a week. Thus it is mostly possible in the recovery phase.
The main protease or SARS CoV Mpro, also known as chymotrypsin-like protease (3CLpro) cleaves at almost 11 sites (Anand et al.,, 2003) on the polyprotein to form the non-structural proteins (nsp) which later combine to form the replicase-transcriptase complex (RTC). Inhibitors acting on this enzyme will cease the process of replication of this viral gene (Wu, Liu, et al.,, 2020). Therefore it is considered to be one of the best choices for drug targets against coronavirus infection. In this study, we performed molecular docking of various known anti-viral drugs in order to predict their potential to be considered as a drug against the SARS CoV–2 infection by looking into the various interactions of these drugs at the active site of the main protease. As a preliminary analysis in the high throughput screening of existing drugs, in silico molecular docking studies help in saving time and the cost involved in laboratory and clinical trials. Since the side effects, maximum dosage to be given, and the metabolic characteristics are known for these existing anti-viral drugs, testing them for the new infection should be given an upper hand.