The outbreak caused by a new species of coronavirus led the World Health Organization (WHO) in early 2020 to declare the disease caused by this virus as a Public Health Emergency of International Importance and soon after it was characterized as a pandemic[1]. In December 2019, in the city of Wuhan, China, an outbreak occurred, in which several individuals went to local hospitals with severe pneumonia of unknown etiology. After investigations to find out about the cause of this outbreak, it was found that most of the initial cases had contact with the same wholesale seafood market[2]. The etiologic agent discovered was a new virus of the family Coronaviridae and genus β-coronavirus and was identified as severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2), which causes coronavirus 2019 or COVID-19, as it became known. In addition, it was shown that, unlike other coronaviruses that infect humans, SARS-CoV-2 has a high human-to-human transmission rate, which was a determining factor for its dissemination[3, 4].
The virus can infect individuals of all ages, however it mainly affects men over 60 years[5]. According to He, Deng and Li[6], the lethality rate is higher in patients with coexisting medical conditions, such as diabetes, hypertension and cardiovascular diseases. Symptoms vary from fever, cough, sore throat, changes in smell and taste to acute respiratory distress syndrome (ARDS) and dyspnoea in the most severe cases[6–8].
The SARS-CoV-2 virus consists of four structures, the spike glycoprotein or S glycoprotein, a membrane protein, an envelope protein and a nucleocapsid protein, which is present within the viral envelope[9]. SARS-CoV-2 is a ribonucleic acid (RNA) virus whose genetic material is a single positive RNA molecule. The virus enters the human host, through the binding of the spike glycoprotein, in the S1 subunit, with its receptor, the angiotensin-converting enzyme 2 (ACE2) that is present on the cell surface[10]. After binding, Furin enzyme will pre-cleave the S glycoprotein in the S1 and S2 subunits and then the transmembrane serine protease 2 (TMPRSS2) enzyme will cleave the S glycoprotein in the S2 subunit. Subsequently, the S2 subunit will assist in the fusion of the viral membrane with the host cell membrane and thus, with the entry of the virus into the host cell[4, 11].
The SARS-CoV-2 main protease is an enzyme called Mpro or 3C-like protease (3CLpro), that plays an important role in the replication cycle, thus becoming a potential target for the control of viral infection[12]. Its action occurs after the virus enters the host cells, where the viral RNA genome will translate inactive proteins, called pp1a and pp1ab, which will be cleaved through Mpro and will result in non-structural proteins and join the RNA to form the virus genome[13]. Thus, it becomes necessary means for inhibiting replication of the SARS-CoV-2 virus. Researchers are seeking out products with efficient antiviral activity to prevent the SARS-CoV-2 virus replication. The peel of pomegranate (Punica granatum), has substantial studies that encompass antibacterial[14], anti-inflammatory[15] and antioxidant[16] activities in addition to antiviral activity agaist Influenza virus[17], Human Immunodeficiency virus (HIV)[18] and Herpes simplex virus[19]. Punicalagin is a phenolic compound present abundantly in pomegranate peel with high molecular weight[20]. Punicalagin is found naturally in two anomeric forms α and β differing from the chiral carbon position (Fig. 1). Recent studies including α/β anomers[21–23] revels that there are differences in the non-covalent interactions profile between these anomers and proteins.
Hence, the present in silico study was aimed to explore the differences in inhibitory potential of α/β anomers of Punicalagin against the main protease viral of SARS-CoV-2 (Mpro).