Immunoinformatics study on the ۳-chymotrypsin like protease (۳CLPro) of SARS-CoV-۲ as a putative antiviral agent

BACKGROUND AND OBJECTIVESLike other coronaviruses, the genome of SARS-CoV-۲ is made from at least ۱۰ open-reading frames (ORFs) which encode ۲ polyproteins (i.e. pp۱a and pp۱ab containing ۱۶ non-structural proteins [nsp]) and accessory proteins. The maturation of these polyproteins is occurred by an auto-proteolytic process mediated by papain-like protease (PLPro/Nsp۳) and ۳-Chymotrypsin like protease (۳CLPro/MPro/Nsp۵). Among this, the ۳CLPro is considered as the SARS-CoV-۲ main protease (MPro) and becomes an attractive candidate for development anti-SARS-CoV-۲ drug candidates. Accordingly, the immunoinformatics properties of SARS-CoV-۲ ۳CLPro were investigated to introduce a potential antiviral agent in the current study.MATERIALS AND METHODSTo perform immunoinformatics study on the SARS-CoV-۲ ۳CLPro as its main protease, its crystal structure was retrieved from the PDB database (PDB code: ۷WQA). Thereafter, this structure was refined to strip the possible heteroatoms and cryopreservative agents. The refined ۳CLPro sequence was analyzed using various web-servers to predict possible linear B-Cell epitopes (BCEs). More investigations are being done to get a comprehensive immunoinformatics study and design an efficient anti-SARS-CoV-۲ vaccine.RESULTS AND DISCUSSIONAccording to the results, Bepipred, Kolaskar & Tongaonkar Antigenicity, Ellipro, ABCPred, SVMtrip, and CBTope algorithms and servers predicted ۹, ۱۱, ۶, ۲۱, ۳, and ۱۴ epitopes in the ۳CLPro, respectively. This indicates the potential of ۳CLPro to elicit host immune system, including the humoral and cellular immune responses. Therefore, more immunoinformatics studies are being performed to predict MHC-۱ and MHC-II binding epitopes and the other properties.CONCLUSIONGiven that SARS-CoV-۲ has a substantially higher mortality rate than other coronaviruses, especially in elderly patients, many diagnostic and therapeutic agents have been introduced to combat this virus. During viral replication, the viral polyproteins (i.e. pp۱a and pp۱ab) synthesized using the host cell translational machinery, are processed by the ۳CLPro and PLpro to generate an active viral replication complex. Hence, these proteases present attractive targets for small molecule inhibitors. Among this, with reference to the high conservancy of ۳CLPro among the ۱۲ different coronaviruses, it has been considered as a good candidate to design pan-inhibitors of viral proteases, especially the SARS-CoV-۲ main protease .

کلیدواژه ها:

SARS-CoV-۲ ، Immunoinformatics ، ۳CLPro ، MPro ، Vaccine design ، Antivirals