A novel bioactive compound shows potential to protect against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and may be the key to developing a broad spectrum antiviral drug for coronavirus, according to data presented at the ASM Microbe 2016 meeting.

A total of 1728 cases of MERS-CoV have been reported from more than 20 countries, and the current mortality rate for MERS-CoV is 36%. However, there is currently no effective antiviral therapy against MERS-CoV available.

Researchers targeted main protease (nsp5), which releases viral nonstructural proteins critical to the replication and transcription process. The protein is conserved among all viruses in the Coronavirus family, including viruses that cause mild, common cold-like symptoms and viruses that cause fatal respiratory distress syndrome like MERS-CoV and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

The researchers screened a chemical library consisting of drug-like small molecules to identify bioactive compounds against MERS-CoV nsp5. Recombinant nsp5 was expressed using the E coli system, and biological activity was verified with fluorescent resonance energy transfer assay. They tested the antiviral activity of 879 compounds against SARS-CoV infection, and they found a compound with >50% inhibition of enzyme activity at the concentration of 50 μg/mL. The compound showed reduced cytopathic effect (CPE) on Vero-E6 cells at 48 hours post-infection, and the 50% inhibitory concentration was 3 μM.


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A plaque assay confirmed that viral titer in a supernatant of Vero-E6 cell culture decreased about 4 logs at 24 hours post-infection at a concentration of 12.5 μM. In addition, cell viability assay showed that 50% cytotoxicity concentration was 75 μM at 48 hours after inoculation.

The selection index of the compound was 25, and western blotting showed that nucleotide protein decreased in a dose-dependent manner in MERS-infected Vero-E6 cells at 24 hours post-infection, indicating that virus replication was reduced.

The researchers noted that the compound reduced virus copies in the cells being infected, but it also reduced viral progenies production in the subsequent rounds of virus replication, which stopped the virus from spreading to healthy, noninfected tissues.

The compound cross-protects against both SARS-CoV and MERS-CoV, which indicates the promising future of developing a broad spectrum antiviral drug for the future outbreak of unknown coronaviruses, the researchers concluded.

Reference

Shuai HP, Yuan S, Zheng B. Screening and identification of a novel compound targeting the main protease(nsp5) against Middle East Respiratory Syndrome coronavirus (MERS-CoV). Presented at the American Society for Microbiology Microbe 2016; June 16-20, 2016; Boston, MA.