Evaluation of small molecule inhibitors for their antiviral activity against EV-A71

Wong, Sie Yeng (2021) Evaluation of small molecule inhibitors for their antiviral activity against EV-A71. Masters thesis, Sunway University.

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Hand, foot, and mouth disease (HFMD) due to enterovirus 71 (EV-A71) infections have been associated with serious neurological complications and high fatality. EV-A71 has become endemic in Asia since 1990s and caused several major outbreaks in the region. In 2018, more than 50,000 HFMD cases and 2 deaths were reported in Malaysia. Yet, no effective licensed antiviral agent is available as a treatment for EV-A71 infection. The main aim of our study was to screen for the antiviral activity of 113 chemical compounds from an antiviral library against EV-A71. In the antiviral screening, we found a potent antiviral candidate, NM107 (2'-C-Methylcytidine), against EV-A71. NM107 showed the highest inhibitory effect (99.97%) to virus plaque formation and reduced the synthesis of viral RNA (99.69%) at the concentration of 100μM in the post-infection assay in vitro. The antiviral activity of NM107 was further investigated through flow cytometry for the evaluation of the intracellular EV-A71 protein levels and the results showed that NM107 was able to down-regulate the intracellular viral protein synthesis. Time of addition assay revealed that the replication of virus was affected during the early stage of viral RNA replication. The virus RNA dependent RNA polymerase is important for the replication of the virus and our molecular docking analysis showed that NM107 could bind to the viral polymerase with high affinity through hydrogen bonding, thus may inhibit the activity of the polymerase. Overall, our study revealed that NM107 inhibited the replication of EV-A71 and reduced intracellular viral protein synthesis in Rhabdomyosarcoma (RD) cells, thus, further in vivo studies with NM107 may be focused for antiviral development against EV-A71.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Hand, foot, and mouth disease; HFMD; enterovirus 71 (EV-A71); antiviral.
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Divisions: Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Dept. Biological Sciences
Depositing User: Ms Yong Yee Chan
Date Deposited: 06 Oct 2023 01:04
Last Modified: 06 Oct 2023 01:04
URI: http://eprints.sunway.edu.my/id/eprint/2439

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