Virtual Screening Multitarget-Based Against 3CL^pro and TMPRSS2 Reveals New Promising Drugs Against SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), responsible for generating COVID-19, has spread worldwide and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020, being responsible for various damages to public health, social life, and the economy of countries. Its high rates of infectivity and mortality have stimulated researchers and pharmaceutical companies to search for new therapies against this disease. The findings in recent years regarding the structure and biochemistry of SARS-CoV2 are remarkable. 3CLpro is a potential target as an anti-SARS agent as it plays a vital role in the viral life cycle. Another promising target is the transmembrane protease serine 2 (TMPRSS2). Recent studies point to TMPRSS2 as one of the main targets responsible for a viral entry related to the cleavage of the S protein. Similar to cathepsins, TMPRSS2 is also responsible for the cleavage of the spike protein SARS-CoV2, which binds to the ACE2 receptor. Also, TMPRSS2 is one of the targets that may represent new alternatives in treating SARS-CoV2. In addition, the multitarget approach has grown in recent years. The design and identification of drugs that act on multiple targets can be the next stage in drug discovery campaigns. Finally, here using a virtual screening protocol docking-based in a multitarget approach, the drugs Raloxifene, Saquinavir, AFP-168, and Valrubicin show a potential inhibition of 3CLpro and TMPRSS2 and can be evaluated in vitro assay to prove your potential