Introduction:Chikungunya Virus (CHIKV), a mosquito-transmitted pathogen, poses a
significant global health threat owing to its widespread prevalence and high morbidity. There are no
approved vaccines or antivirals for prevention or treatment. Screening of folklore medicinal plants
has emerged as a promising approach to finding novel therapeutics to combat pathogens. Hence, this
study aimed to evaluate the anti-chikungunya potential of folklore medicinal plants and their phytochemicals.Methods:Maximum non-toxic concentrations (MNTD) of the extracts to Vero cells were determined
by the cytotoxicity assay. A Focus-Forming Unit (FFU) assay was used to assess the antiviral activity
of the extracts (at MNTD) against CHIKV in Vero cells under pre-, co-, and post-treatment conditions.
GC-MS was used to detect the phytochemicals of the extracts, and Schrodinger (Maestro) software
was employed for their molecular docking against the target protein of CHIKV.Results:Azadirachta indica exhibited anti-CHIKV activity during pre- and post-treatment, decreasing
the virus titer from 8.145 to 7.998 and 8.361 to 8.040 mean log10 FFU/ml, respectively. Calendula
officinalis and Piper retrofractum exhibited anti-CHIKV activity only during post-treatment (8.361
to 8.135, 8.361 to 8.075). Moreover, molecular docking studies of phytochemicals detected in GCMS
analysis of all the extracts revealed that many phytochemicals (especially F3, F5, F6, and A1)
could bind to the non-structural protein (nSP2) target of CHIKV and suppress the viral replication.Conclusion:The screened plants showed the ability to inhibit CHIKV infection and replication and
hold potential for further investigation in developing treatments for Chikungunya.