Aims Coronavirus disease 2019 (COVID-19) has appeared in Wuhan, China but the fast transmission has led to its widespread prevalence in various countries, which has made it a global concern. Another concern is the lack of definitive treatment for this disease. The researchers tried different treatment options which are not specific. The current study aims to identify potential small molecule inhibitors against the main protease protein of SARS-CoV-2 by the computational approach. Main methods In this study, a virtual screening procedure employing docking of the two different datasets from the ZINC database, including 1615 FDA approved drugs and 4266 world approved drugs were used to identify new potential small molecule inhibitors for the newly released crystal structure of main protease protein of SARS-CoV-2. In the following to validate the docking result, molecular dynamics simulations were applied on selected ligands to identify the behavior and stability of them in the binding pocket of the main protease in 150 nanoseconds (ns). Furthermore, binding energy using the MMPBSA approach was also calculated. Key findings The result indicates that simeprevir (Hepatitis C virus NS3/4A protease inhibitor) and pyronaridine (antimalarial agent) could fit well to the binding pocket of the main protease and because of some other beneficial features including broad-spectrum antiviral properties and ADME profile, they might be a promising drug candidate for repurposing to the treatment of COVID-19. Significance Simeprevir and pyronaridine were selected by the combination of virtual screening and molecular dynamics simulation approaches as a potential candidate for treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) has been first appeared in Wuhan, China but its fast transmission, led to its widespread prevalence in various countries and make it a global concern. In addition, lack of a definitive treatment is another concern that needs to be attention. Researchers have come up with several options, which are not certain, but protease inhibitor and some antiviral agent are in the forefront. In this study a virtual screening procedure employing docking of different databases including 1615 FDA approved drugs was used to identify new potential small molecule inhibitors for protease protein of COVID-19. The docking result indicates that among all, simeprevir (Hepatitis C virus (HCV) NS3/4A protease inhibitor) could fit well to the binding pocket of protease and because of some other positive features including ADME profile, might be a helpful treatment option for COVID-19.

Local chemotherapy with biocompatible drug-delivery systems prolongs survival in patients. Due to the biocompatibility and high loading capacity, bentonite nanoclay is a good candidate for the fabrication of drug-delivery vehicles. In this study, doxorubicin-bentonite nanoclay complex (DOX-Bent complex) was prepared for the first time as a sustained-release drug-delivery system for intratumoural chemotherapy of melanoma. An efficient loading of DOX on 1 mg of bentonite nanoclay as high as 994.45 ± 4.9 µg was obtained at a 30:1 DOX:bentonite nanoclay mass ratio. The DOX-Bent complex showed a low initial burst release of DOX in the first 24 h of release, followed by a sustained-release pattern for 21 days. The cumulativein vitrorelease of DOX from the DOX-Bent complex at pHs 6.5 and 7.4 revealed that the DOX-Bent complex can distinguish between tumour and normal tissues and express specific drug release at the tumour site. The results of cytotoxicity experiments indicated that the release pattern of DOX can supply sufficient DOX to inhibit growth of the melanoma cancer cell with an IC50 of 0.29 ± 0.07 µg/mL. It is thus suggested that the DOX-Bent complex be introduced as a drug-delivery system for effective local cancer therapy.

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