Recent progress in the development of potential drugs against SARS-CoV-2

Abstract

SARS-CoV-2, a newly emerged and highly pathogenic coronavirus, is identified as the causal agent of Coronavirus Disease (2019) (COVID-19) in the late December 2019, in China. The virus has rapidly spread nationwide and spilled over to the other countries around the globe, resulting in more than 120 million infections and 2.6 million deaths until the time of this review. Unfortunately, there are still no specific drugs available against this disease, and it is very necessary to call upon more scientists to work together to stop a further spread. Hence, the recent progress in the development of drugs may help scientific community quickly understand current research status and further develop new effective drugs. Herein, we summarize the cellular entry and replication process of this virus and discuss the recent development of potential viral based drugs that target bio-macromolecules in different stages of the viral life cycle, especially S protein, 3CL^Pro, PL^Pro, RdRp and helicase.

Keywords: Coronavirus; Entry inhibitors; Protease inhibitors; SARS-CoV-2.

Fig. 1

The cell entry and replication process of SARS-CoV-2. The combination of the spike protein (S) and the host cell receptor-ACE2 leads to fusion of the viral and cell membranes. Proton influx into the endosome and cathepsins will trigger the membrane fusion activity in S protein and facilitate endosomal cellular entry of CoV. In contrast, the S protein is cleaved to form S1 and S2 subunit to facilitate the non-endosomal cellular entry of CoV. After the viral RNA is released, ORF1a and ORF1ab are translated into Pp1a and Pp1ab, which are processed by 3CL^Pro and PL^Pro to produce NSPs. Subsequently, mRNAs that synthesized with the catalytic of RdRp are translated to produce the structural and accessory proteins, while newly synthesized genomic RNA is assembled by N protein to form helical nucleocapsid. After that, the structural proteins including S, E, and M are inserted into the ER and then move along the pathway into the ERGIC, where the interactions between the helical nucleocapsid and the structural proteins are occurred to form the assembled virion. Finally, virion is transported to the cell surface by intracellular vesicles and released across the plasma membrane by exocytosis.