In preclinical studies, a new pan-coronavirus papain-like protease (PLpro) inhibitor has shown a near complete reduction in SARS-CoV-2 viral load in the lungs.
Infex Therapeutics has selected the clinical candidate for its in-house COV-X programme based on this in vivoefficacy data in a murine SARS-CoV-2 model.
The pre-clinical study aimed to assess the efficacy and safety profile of COV-X against main protease (Mpro) inhibitor nirmatrelvir and a control group (saline vehicle only). Two dosing regimens were utilised: 100mg/kg and 200mg/kg.
In five of the six samples dosed with COV-X at 200mg/kg, viral load in the lungs was below the limit of detection. Even at doses five times lower than nirmatrelvir, COV-X provided protection from lung damage. COV-X also demonstrated a superior drug metabolism and pharmacokinetics (DMPK) profile to nirmatrelvir.
COV-X targets the key coronavirus PLpro enzyme, which is essential for viral replication and evasion of host immune response. As a result, the drug has the potential for broad spectrum efficacy against new coronaviruses or variants with pandemic potential.
Furthermore, development of new variants of SARS-CoV-2 that are resistant to nirmatrelvir have been reported widely in recent weeks, with further cross resistance to other drugs in the Mpro class.
Dr Peter Jackson, CEO of Infex Therapeutics, commented: “With global SARS-CoV-2 vaccines showing increasing weakness against new variants, it will be essential to develop effective broad-spectrum antivirals that can future-proof against new coronaviruses with pandemic potential. Following encouraging pre-clinical data in comparison with Pfizer’s Mpro inhibitor nirmatrelvir, we have high hopes for our nominated candidate for our COV-X programme.”
Edited by Diana Spencer, Senior Digital Content Editor, Drug Discovery World