Triazole, imidazole, and thiazole-based compounds as potential agents against coronavirus

Abstract

The expansion of the novel coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), COVID-19 (coronavirus disease 2019), or 2019-nCoV (2019 novel coronavirus) is a global concern over its pandemic potential. The need for therapeutic alternatives to stop this new pandemic is urgent. Nowadays, no efficacious therapy is available, and vaccines and drugs are underdeveloped to cure or prevent SARS-CoV-2 infections in many countries. Some vaccines candidates have been approved; however, a number of people are still skeptical of this coronavirus vaccines. Probably because of issues related to the quantity of the vaccine and a possible long-term side effects which are still being studied. The previous pandemics of infections caused by coronavirus, such as SARS-CoV in 2003, the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, HCoV-229E, and HCoV-OC43 were described in the 1960 s, -HCoV-NL63 isolated in 2004, and HCoV-HKU1identified in 2005 prompted researchers to characterize many compounds against these viruses. Most of them could be potentially active against the currently emerging novel coronavirus. Five membered nitrogen heterocycles with a triazole, imidazole, and thiazole moiety are often found in many bioactive molecules such as coronavirus inhibitors. This present work summarizes to review the biological and structural studies of these compound types as coronavirus inhibitors.

Keywords: Coronavirus; Enzyme; Imidazole; Thiazole; Triazole.

Fig. 1

(A) Taxonomy of the family Coronaviridae, Human coronaviruses are shown in bold type. Highly pathogenic human coronaviruses are shown in red type. Human coronaviruses belong to two different genera: Betacoronavirus and Alphacoronavirus . (B) Structure of the SARS-CoV-2 virion gRNA: genomic RNA; N: nucleocapsid protein; S: spike; E: envelope; and M: membrane . (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

1,2,3-(A) 1,2,4-(B) triazole-based as potential anticoronavirus respectively , , , , , , , , , .

Fig. 3

Compound 23 at the active site of the protein (A) and in the active site of the protein making HB and pi-pi interactions (B) .

Fig. 4

Compound 24 at the active site of the protein (A) and in the active site of the protein making HB and pi-pi interactions (B)

Fig. 5

Compound 25 at the active site of the protein (A) and of the active site of the protein making HB and pi-pi interactions (B) .

Fig. 6

Imidazole-based as potential SARS-CoV inhibitors , , , .

Fig. 7

X-ray crystal structure of compound 44 in SARS-CoV 3CLpro active site (PDB code: 4TWW)

Fig. 8

Thiazole-based as potential coronavirus , , , , .

Fig. 9

A) a close view of the interactions between SARS-associated coronavirus main protease (white cartoon) with ritonavir (yellow-ball stick). B) The binding pockets (pink-ball stick) of SARS-associated coronavirus main protease with ritonavir (yellow space fill) .