In Vitro Inhibition of Zika Virus Replication with Amantadine and Rimantadine Hydrochlorides

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus in which human infection became relevant during recent outbreaks in Latin America due to its unrecognized association with fetal neurological disorders. Currently, there are no approved effective antivirals or vaccines for the treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV reference strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the latter. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine the potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across flavivirus, susceptible to be blocked by modified more specific adamantane compounds.

Amantadine and Rimantadine Analogues—Single-Crystal Analysis and Anti-Coronaviral Activity

“…The established MTC values for the derivative compounds 1A and 1R of the ion-channel inhibitors Amantadine and Rimantadine are 400 µg/mL. The results obtained by us for the toxicity of compounds 1A and 1R are similar to the results obtained by other author groups using another cell line for the toxicity of Amantadine and Rimantadine [40]. The determined CC50 is above 400 µg/mL.…”

Nascent pharmacological advancement in adamantane derivatives

“…Arias et al have reported in vitro antiviral efficacies of amantadine and rimantadine hydrochlorides against ZIKV strains (ZIKV CIET‐01, ZIKV MR766, and ZIKV R103451), DENV‐1 Angola, and YFV 17D. [ 100 ] Compound 51 displayed maximum efficacies toward ZIKV CIET‐01 and ZIKV R103451. Chayrov et al have synthesized a class of amino acids substituted adamantane derivatives and evaluated their antiviral activity against influenza virus A (H3N2).…”