Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2
Figure 4
CID15997213 targets viral nsP2.
(A) Time of addition study. Test compound, CID15997213, was added to the designated wells by replenishing the culture media with fresh culture media containing 5 µM of the compound at the time points denoted on the x axis. The graph denotes the virus titers at 16 hours post-infection from various time of addition points. Each data point is the mean from two independent replicates with duplication in titration. (B) Location of the mutations in the CID15997213 resistant viruses. The mutations mapped within the N-terminus of nsP2 protein (pink). There were no missense mutations in either nsP1, nsP3 or nsP4 genes. * Methyl-transferase like domain. (C) Sequence alignment of nsP2 alphaviruses. Amino acid sequences of nsP2 of following alphaviruses were aligned with Clustal W (www.clustal.org): VEEV (L01442.2, GenBank Access No. hereafter), EEEV (NC_003899), WEEV (NC_003908), Fort Morgan virus (FMV, NC_013528), Ross River virus (RRV, NC_001544), Semliki Forest virus (SFV, NC_003215), O'nyong-nyong virus (ONYV, NC_001512.1), CHIKV (L37661.3), Sindbis virus (SINV, NP_740671.1). Y102 position is highlighted in red.