Ciprofloxacin and moxifloxacin could interact with SARS-CoV-2 protease: preliminary in silico analysis

Abstract

Background A large body of research has focused on fluoroquinolones. It was shown that this class of synthetic antibiotics could possess antiviral activity as a broad range of anti-infective activities. Based on these findings, we have undertaken in silico molecular docking study to demonstrate, for the first time, the principle for the potential evidence pointing ciprofloxacin and moxifloxacin ability to interact with COVID-19 Main Protease. Methods In silico molecular docking and molecular dynamics techniques were applied to assess the potential for ciprofloxacin and moxifloxacin interaction with COVID-19 Main Protease (Mpro). Chloroquine and nelfinavir were used as positive controls. Results We revealed that the tested antibiotics exert strong capacity for binding to COVID-19 Main Protease (Mpro). According to the results obtained from the GOLD docking program, ciprofloxacin and moxifloxacin bind to the protein active site more strongly than the native ligand. When comparing with positive controls, a detailed analysis of the ligand–protein interactions shows that the tested fluoroquinolones exert a greater number of protein interactions than chloroquine and nelfinavir. Moreover, lower binding energy values obtained from KDEEP program were stated when compared to nelfinavir. Conclusions Here, we have demonstrated for the first time that ciprofloxacin and moxifloxacin may interact with COVID-19 Main Protease (Mpro).

Repurposing of antibiotics for clinical management of COVID-19: a narrative review

“…Studies have demonstrated the potential action of fluoroquinolones for the treatment of SARS-CoV-2 associated pneumonia and called for randomized clinical trials of respiratory fluoroquinolones such as ciprofloxacin, moxifloxacin and levofloxacin [ 64 , 65 ]. Interestingly, these drugs were also recommended in the treatment of community-acquired pneumonia in COVID-19 patients [ 66 ].…”

The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)—preliminary molecular docking analysis

“…The urgent need for an effective inhibitor of crucial viral proteins is the reason for development of new testing techniques. Recently it was shown by us that ciprofloxacin and moxifloxacin could interact with COVID-19 Main Protease (M pro ) [ 14 ].…”

“…What is important, these effects were seen at the clinically achievable concentrations and may result from one common mode of action: the inhibition of type II topoisomerases or inhibition of viral helicases [ 13 ]. Previously we have demonstrated for the first time that ciprofloxacin and moxifloxacin may interact with COVID-19 Main Protease (M pro ) pointing the basis for further in vitro as well as in vivo analysis underlying the two already-marketed fluoroquinolones derivatives repositioning to treat SARS-CoV-2 infections [ 14 ]. In this study, we used molecular docking strategies to repurpose fluoroquinolone derivatives—ciprofloxacin and levofloxacin for COVID-19.…”

The potential role of Fluoroquinolones in the management of Covid-19 a rapid review

“…moxifloxacin), binds to and inhibits SARS-CoV-2 M pro , consequently prevent its replication. [69] Interestingly the interaction of FQs with M pro suggested being stronger compared to other protease inhibitors namely nelfinavir and chloroquine.…”