Druggable targets from coronaviruses for designing new antiviral drugs

Abstract

Graphical abstract

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

“…Several structural and non-structural proteins required for its replication, catalyzed by Main protease (Mpro) also known as 3-chymotrypsin-like protease (3CLpro) and by papain-like protease (PLpro) shall be executed through mRNA to facilitate the multiplication of virus [7] . All these proteins can serve as druggable targets against COVID-19 in search of SARS CoV-2 inhibitors [8] , [9] , [10] .…”

Main Chemotypes of SARS-CoV-2 Reproduction Inhibitors

“…The problem stimulates innovations and drives, in part, the development of both medicinal chemistry and modern organic synthesis. The urgency of the problem has prompted chemical community to perform in silico analysis the affi nity of compounds in the existing libraries for the known SARS-CoV2 targets [2][3][4][5][6][7] and urgently consider the possibility of repurposing existing drugs [3,4,[8][9][10][11][12][13][14][15][16][17]. In view of the sharply increased global demand, there is an urgent need for the development and scaling of new methods of synthesis, as well as costeffective technological solutions for the production of antiviral pharmaceutical substances [18][19][20].…”

“…In general, pyrimidine derivatives are more active than purine derivatives. In this group, a particular place belongs to pyrrolo[2,1-f] [1,2,4]triazine derivative 62 [75,76] (remdisivir), which is actually a prodrug. Evidence for the effi ciency of remdisivir 62 was obtained in clinical trials, and it already actively used in medical practice.…”

Synthetic and computational efforts towards the development of peptidomimetics and small-molecule SARS-CoV 3CLpro inhibitors

“…To combat the current outbreak of COVID-19, the scientific community is trying to develop effective treatment within a feasible time. Many well-established strategies are taken by the research organizations to eradicate the COVID-19 pandemic 16 , 17 . In the field of drug discovery and development, repurposing of existing drugs is one of the organized and economic strategies to fight against novel diseases, like novel coronavirus 18 .…”