Computational Repurposing of Molecules Against SARS‐CoV‐2 Orf3a Protein as Potential Adjuvants to Treat SARS‐CoV‐2 Viral Infection

Abstract Humanity has suffered from the COVID‐19 pandemic caused by SARS‐CoV‐2 virus creating a necessity to develop therapeutic targets to treat this deadly virus. The SARS‐CoV‐2′s Orf3a protein is considered a potential target for drug development because of its functions over several cellular mechanisms that condition the propagation of the infection (mainly to egress cell material). The development of new drugs using the Orf3a as a target is challenging due to its intracellular location making it difficult to approach in comparison with other surface proteins. This study proposes potential molecules for the development of a new drug against Orf3a which can be used as an adjuvant against SARS‐CoV‐2 infection. We performed molecular docking using two libraries of compounds (FDA‐approved drug and Bioactive molecules list) directed to interact in the region between amino acids (Leu65, Lys66, Arg68, Asn137, Tyr141, Asn144, Tyr154, Cys157, Pro159, Asn161, Glu181, Gly188, Tyr189, Glu191, Lys192, and Glu194) in the Orf3a protein belonging to the SARS‐CoV‐2 virus. We propose these molecules because of their potential effect on reducing Orf3a´s functions over endosomes by reducing vesicle secretion from cells infected with this virus. Therefore, these results represent an important contribution to the development of new drugs to combat this type of virus.