SARS-CoV-2 is a positive-sense single-stranded RNA coronavirus. This virus can cause severe acute respiratory syndrome and spreads between people through aerosols and respiratory droplets. It broke out in early 2020, causing a massive epidemic contagious disease, called COVID-19 (Coronavirus disease 2019). The symptoms of COVID-19 are fever, cough, headache and even loss of smell and taste. Sadly, this disease has disrupted the rhythm of life for most people around the world.

Except for humans, other species, like cats, ferrets, and hamsters, are susceptible to SARS-CoV-2 as well. SARS-CoV-2 is highly contagious and deadly. Because of its high infectivity, kinds of variants have emerged, including alpha, beta, gamma delta, and omicron. Therefore, the development of inhibitors and vaccines for the virus is a vital subject.

MMT5-14 is a potent SARS-CoV-2 pan inhibitor.

MMT5-14 is a Remdesivir analogue, possessing a better antiviral activity in four variants of SARS-CoV-2 than its lead compound. It can inhibit SARS-CoV-2 and its 4 variants α, β, γ and δ, exhibiting EC50 values of 0.4 μM, 2.5 μM, 15.9 μM, 1.7 μM and 5.6 μM. In animal experiments, MMT5-14 shows higher stability than Remdesivir in microsomes. Besides, the inhibitor (10 mg/kg; i.v.; single dosage) has higher concentrations of prodrugs and active metabolites in the blood and lungs after 4 hours of injection in hamsters. In addition, MMT5-14 increases tissue exposure in most of the tissues and possesses 5- to 10-fold higher tissue selectivity in the lungs compared to Remdesivir.

In conclusion, MMT5-14 is a potent SARS-CoV-2 pan inhibitor and has better antiviral properties than Remdesivir. MMT5-14 can be a potential antiviral agent for research on COVID-19.

Hu H, et al. J Med Chem. 2022 Sep 22;65(18):12044-12054.