In vitro Study of Antiviral Activity of Mycophenolic Acid on Brazilian Orthobunyaviruses

Abstract

Objective: Oropouche, Caraparu, Guama, Guaroa and Tacaiuma are ssRNA viruses that belong to the genus Orthobunyavirus and have been associated with human febrile illnesses and/or encephalitis. In this study, we evaluated the antiviral action of mycophenolic acid (MPA) on theseorthobunyaviruses to achieve a therapeutic agent to treat the diseases caused by these viruses. Methods: The in vitro antiviral evaluation to MPA was done by using plaque assay at different periods of treatment. Results: Results showed that MPA at a concentration of 10 µg/ml has significant antiviral activity on Tacaiuma virus when treatment was initiated either 24 h before or 2 h after viral infection. Moreover, MPA has an inhibitory effect on Guama virus replication, but only when treatment was initiated before cell infection. Addition of guanosine in the culture reverted the inhibitory effect of MPA on Tacaiuma and Guama viruses, suggesting that the antiviral activity of this substance was via depletion of the intracellular guanosine pool. Conclusion: Our results suggest that MPA would not be a good therapeutic agent to treat the diseases caused by Oropouche, Caraparu, Guama, Guaroa, and Tacaiuma viruses.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…Other Flavivirus susceptible to MMF are dengue virus type 2, Yellow fever virus 17D, Modoc virus, and Montana myotis leukoencephalitis virus [139][140][141]. Some studies report anti-viral effect of the drug against other several different RNA viruses including Chikungunya [142,143], smallpox virus, foot-andmouth disease virus (FMDV [144], peste des petits ruminants virus (PPRV) [145], Junin virus [146], norovirus [147], the arenavirus causative agent Lassa's hemorrhagic fever [148], the reovirus [149,150] and others [151,152].…”

Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality

“…Mycophenolic acid is a non-nucleoside, non-competitive, reversible inhibitor of eukaryotic IMP dehydrogenase, and has been reported to inhibit multiple viruses, including bunyaviruses, arenaviruses and flaviviruses. [64][65][66] Quantification of SFTSV, GTV and HRTV vRNA by qRT-PCR Cells were harvested and the total cellular mRNA was extracted by using the QIAamp Viral RNA Mini Kit (Qiagen), according to the manufacturer's instructions. For quantitation of vRNA, a standard curve was constructed with a plasmid containing full-length nucleotides of the S gene of the respective virus, and qRT-PCR was performed with the One-step Primer Script RT-PCR Kit (Takara) in a LightCycler 480 (Roche).…”

Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery

“…MPA is more potent to inhibit type II than type I IMPDH enzyme, the former type expresses in activated lymphocytes, while the latter one in other most cells ( Allison and Eugui, 2000 ). DNA or RNA virus replication replies on host guanosine pool, thus, MPA shows a broad spectrum antiviral activity against a variety of viruses, including HIV ( Chapuis et al, 2000 ), HEV ( Wang et al, 2014 ), HBV ( Gong et al, 1999 ), BK polyoma virus ( Acott et al, 2009 ), HCV and flaviviruses (DENV, WNV, JEV, and ZIKA) ( Diamond et al, 2002 ; Morrey et al, 2002 ; Henry et al, 2006 ; Sebastian et al, 2011 ; Ye et al, 2012 ; Barrows et al, 2016 ; Adcock et al, 2017 ), orthobunyaviruses (Guama and Tacaiuma viruses) ( Livonesi et al, 2007 ), orthopoxviruses like Vaccinia virus (VacV) and cowpox ( Smee et al, 2001 ), rotavirus ( Chan et al, 2013 ), SINV ( Scheidel and Stollar, 1991 ), IAV ( To et al, 2016 ; Cho et al, 2017 ; Hui et al, 2018 ), and MERS-CoV( Chan et al, 2013 ) ( Table 4 ).…”