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Mayaro Virus Antiviral EIDD-1931

Mayaro virus is a mosquito-borne virus endemic to forests in South America. It causes acute illness with fever, headache, rash, and long-lasting joint pain. Mayaro’s range could spread in the future because of climate change. No vaccines or antiviral drugs are currently available although there are some candidates under development.

Therefore, a concerned team of scientists from the Rega Institute for Medical Researchin Belgium wanted to do exploratory research on antivirals that might treat this disease. They chose a panel of molecules that are known to treat other mosquito-borne viruses, some of which block early stages of the virus life cycle (arbidol, chloroquine, suramin, and ribavirin), and some that inhibit virus genome replication (favipiravir, 7DMA, 2’CMC, EIDD-1931, galidesivir and remdesivir).

They then applied these selected molecules to a model of cell culture that was infected with Mayaro virus. The researchers measured the 50% effective concentration, or the amount of molecule that inhibits 50% of the virus infectivity. They optimized the antiviral screening assay to be reproducible and reliable.

The assay described in this paper can be useful to test future antiviral drugs against this virus. Furthermore, the three molecules that performed well in cell culture are worth further study with in vivo models. Although the range of Mayaro virus is limited for now, we should study it and other neglected diseases to proactively prevent suffering in the future.

 

Langendries L, Abdelnabi R, Neyts J, Delang L. Repurposing drugs for Mayaro virus: identification of EIDD-1931, Favipiravir, and Suramin as Mayaro virus inhibitors. Microorganisms. 2021 Mar 31;9(4):734. PMID: 33807492

Protease Inhibitors: Saquinavir and Boceprevir

The COVID-19 pandemic continues to cause death and severe illness around the world. As many countries still experience vaccine shortages and the virus evolves to be more contagious, we need to develop better treatments for this disease.

A Possible Target:

The SARS-CoV2 main protease (Mpro) is an attractive target for drug treatment. The coronavirus needs this protease to process its proteins, an important step in its life cycle. Protease inhibitors are already in clinical use to treat other viral infections, such as HIV and hepatitis C. Repurposed existing drugs can get approval to treat disease faster than new drugs because their safety and pharmacokinetics are already known. Can we repurpose known protease inhibitors to treat SARS-CoV2 infection?

Two recent scientific studies address this question.

Docking and Molecular Dynamics Simulations:

Bello et al. built a computer model of Mpro and twelve promising protease inhibitors: darunavir, indinavir, saquinavir, tipranavir, diosmin, hesperidin, rutin, raltegravir, velpatasvir, ledipasvir, rosuvastatin, and bortezomib. The model predicts that of the twelve, saquinavir should bind to Mpro the best. Interestingly, saquinavir has long been used as part of drug cocktails to treat HIV. Although a computer study is limited, saquinavir is worth following up in vitro.

Enzyme Assays:

Another team of researchers, Ma et al., used an enzyme assay to screen for drugs that might inhibit the activity of Mpro. Out of a library of known inhibitors, they found that boceprevir inhibited Mpro the most. Formerly, boceprevir was used to treat hepatitis C before more effective protease inhibitors were developed. Boceprevir might find new life now as a treatment for COVID-19, and is worth further study.

 

Bello M, Martinez-Muñoz A, Balbuena-Rebolledo I. Identification of saquinavir as a potent inhibitor of dimeric SARS-CoV2 main protease through MM/GBSA. Journal of Molecular Modeling. 2020 Nov 12; 26(12):340. PMID: 33184722

Ma C, Sacco MC, Hurst B, et al. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV2 viral replication by targeting the viral main protease. Cell Research. 2020 Aug; 30(8):678-692. PMID: 32541865