Autor(es): Rothan Hussin A, Bahrani Hirbod, Mohamed Zulqarnain, Teoh Teow Chong, Shankar Esaki M, Rahman Noorsaadah A, Yusof Rohana

Resumo: Lack of vaccine - effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives - other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other h-, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease - E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 - -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY - RIBA was determined to be 10.95±2.12 ?M - 15.51±1.62 ?M respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 ?M. When compared, DOXY showed higher inhibition of viral infectivity - entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication - attenuated its infectivity in vivo. Further experimental - clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.

Imprenta: PloS One, v. 10, n. 5 , p. e0126360, 2015

Identificador do Objeto Digital: 10.1371/journal.pone.0126360

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever

Data de Publicação: 2015