Didemnins Inhibit COVID-19 Main Protease (Mpro)

The novel coronavirus disease because of infection with the SARS-CoV-2 virus, COVID-19, was first appeared in Wuhan, China, in December 2019. It has spread rapidly all around the World and has been accepted as a pandemic. Specific therapies for COVID-19 treatment is not available for now. Thus, there is a huge effort to develop and discover new therapeutic agents and vaccines by scientists. The design and development of new therapeutic agents for treatment through medicinal chemistry is slow and needed a hard labor process. Thus, it is urgent to achieve the discovery of more effective agents. Marine natural products have antiviral activity and quite significant pharmacological capacity. The antiviral properties of these products are shown as new promising therapeutic alternatives against the viruses. The present work aimed to assess the inhibition potential of Didemnin A, B, and C isolated from tunicates to COVID-19 Mpro protein through a molecular docking method. The molecular characterization of compounds with binding affinity was performed by using the Swiss Target Prediction Method. As a result, the binding energy of Didemnins A, B, and C was calculated as -11.82 kcal/ mol, -10.27 kcal/ mol, and -9.26 kcal/ mol, respectively. Also, the docking studies showed that Didemnin B involved in hydrogen bonding with Glu166 in the active site of the Mpro protein. Therefore, the natural marine compounds have the potential for developing drugs against to SARS-CoV-2 virus, which may aid in overcoming the clinical challenge of the COVID-19 pandemic.