Just a glitch. I've made that mistake several times. Always get corrected.

By YOU, actually! This is your thing!

Thanks for the correction. I'll check the links! Always appreciate links.

Also, my understanding is truly limited. My brain is 67 years old. Doing the best I can. 😁

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https://www.sciencedirect.com/science/article/pii/S0188440920308638

Taking all these data together, it is now apparent that inhibitors of the nsp13 activity offer potential therapeutic option for coronavirus including SAR-CoV-2. Among the various approaches of nsp13 activity inhibition are targeting ATP binding or direct NTPase activity, nucleic acids binding to the helicase, blocking helicase translocation, etc. The class of compounds identified with a promise through such mechanisms include benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and bananin derivatives (8). For example, bananins have been shown to inhibit SARS-CoV ATPase activity leading to inhibition of viral replication in vitro with IC50 values far less than 10 mM (9). On these bases, studies on the potential of viral helicase inhibitors in SARS-CoV-2 infection or COVID-19 is well justified.

https://content.sciendo.com/configurable/contentpage/journals$002facph$002f70$002f2$002farticle-p145.xml

Helicases are proteins that catalyze the separation of duplex oligonucleotides into single strands exploiting the derived energy from ATP hydrolysis (11).

The MERS-CoV helicase non-structural protein 13 (M-nsp13) is a critical component for viral replication and is presently viewed as a possible drug target for potential coronavirus chemical inhibitors (12). Its substrates are double-stranded RNAs (dsRNA). The main mode of action is the unwinding of a substrate in a process depending mainly on ATP gradient in a 5’-to-3’ direction. Length of the 5’ loading strand of the partially duplex RNA substrate is another factor playing a crucial role affecting the efficiency of the unwinding reaction (13). Because of all these helicase functions, MERS helicase is considered a powerful antiviral target.

Triazoles are versatile heterocyclic moieties with a broad spectrum of pharmacological activities (14). He and coworkers (15) reported that triazole derivatives had shown potency as antiviral agents against H1N1influenza virus. The 1, 2, 4-triazole derivative was found to show the best activity against influenza B among all of compounds evaluated in a study by Zhao and Aisa (16). A limited number of possible inhibitors of nsp13 have been explored (17). SSYA10-001 is a 1, 2, 4-triazole derivative which was reported as an nsp13 non-competitive inhibitor through the blockage of SARS and MERS-CoV replication. It was postulated that SSYA10-001 binding pocket of SARS-CoV nsp13 is preserved among different coronavirus helicases, indicating the discovery of broad-spectrum coronavirus inhibitors. SSYA10-001was reported as potential effective inhibitor of viral replication in MERS-CoV replicon (Fig. 1) (18). All the above mentioned prompted us to design and synthesize new 1, 2, 4-triazole derivatives in order to be screened as helicase inhibitors that simply prevent the replication of MERS-CoV.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271831/

Bismuth Salts Inhibit the NTPase and RNA Helix-Unwinding Activities of SARS-CoV-2 Nsp13 As aforementioned, we have observed that certain divalent cations, like Ca2+ and Zn2+, did not support RNA helix unwinding by SARS-CoV-2 nsp13, while high concentrations of Mg2+ showed inhibitory effect (Fig. 3C, ​C,3D).3D). Moreover, previous studies reported that some bismuth salts could inhibit the NTPase and RNA helicase activities of SARS-CoV nsp13 as well as the replication of SARS-CoV in cells (Yang et al.2007a, b). Therefore, we sought to examine whether NTPase and RNA helix-unwinding activities of SARS-CoV-2 nsp13 can also be inhibited by the bismuth salts. Here, we used three different bismuth salts, including bismuth potassium citrate (BPC), ranitidine bismuth citrate (RBC), and bismuth citrate (BC). BPC and RBC are originally used to treat the gastrointestinal diseases, and BC is the intermediate of BPC. Our data showed that all these bismuth salts inhibited the ATPase activity of SARS-CoV-2 nsp13 at 10 μmol/L, as BPC and RBC showed stronger inhibitory effects than BC (Fig. 5A). Moreover, we found that 10 μmol/L BPC or RBC almost abolished the RNA helix unwinding activity of nsp13 (Fig. 5B, lanes 4 and 5); on the other hand, although BC treatment also effectively inhibited the RNA helicase activity of nsp13, its inhibitory efficiency was in much less than BPC or RBC (Fig. 5B, lane 6). To further characterize the inhibitory effect of BPC or RBC on the NTPase and RNA helicase activities of SARS-CoV-2, we treated recombinant nsp13 with increasing concentrations of either bismuth salts. Our data show that either BPC or RBC could inhibit the ATPase and helicase activities of MBP-nsp13 in a dose-dependent manner (Fig. 6).

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