RESUMEN
The discovery and development of novel antiviral drugs from natural sources is continuously increasing due to limitations of currently available drugs such as toxic side effects, drug residue risk factors, high costs, and poor therapeutic strategies. Also, there are very few known antiviral drugs that are effective against only specific viruses. Hence, the present study is intended to isolate and characterize potent antiviral compounds from the methanolic root extract of Sophora interrupta Bedd. against avian paramyxovirus, Newcastle disease virus (NDV) and to distinguish the molecular basis of antiviral compounds. The two isolated flavonoids, maackiain (SR-1) and echinoisoflavanone (SR-2) exhibited the best antiviral activities against NDV infection in chicken embryo fibroblast cell lines compared to the standard antiviral drug, Ribavirin. Further, the in vitro studies and quantitative PCR analysis suggests that these flavonoids inhibit the viral entry, replication, and transcription, which may be beneficial as a promising strategy for the treatment of viral infections. Besides, the molecular docking studies of SR-1 and SR-2 exhibited high binding affinities of -7.6 and -8.0 kcal mol-1, respectively, and marked interactions with the NDV surface glycoprotein, hemagglutinin neuraminidase (HN). Also, the in silico toxicity properties as well pharmacokinetic studies of isolates revealed them as pharmacologically potent antiviral compounds.
RESUMEN
The complete genome consensus sequence was determined for avian paramyxovirus (APMV) serotype 9 prototype strain PMV-9/domestic Duck/New York/22/78. The genome is 15,438 nucleotides (nt) long and encodes six non-overlapping genes in the order of 3'-N-P/V/W-M-F-HN-L-5' with intergenic regions of 0-30 nt. The genome length follows the "rule of six" and contains a 55-nt leader sequence at the 3' end and a 47-nt trailer sequence at the 5' end. The cleavage site of the F protein is I-R-E-G-R-I downward arrowF, which does not conform to the conventional cleavage site of the ubiquitous cellular protease furin. The virus required exogenous protease for in vitro replication and grew only in a few established cell lines, indicating a restricted host range. Alignment and phylogenetic analysis of the predicted amino acid sequences of APMV-9 proteins with the cognate proteins of viruses of all five genera of family Paramyxoviridae showed that APMV-9 is more closely related to APMV-1 than to other APMVs. The mean death time in embryonated chicken eggs was found to be more than 120h, indicating APMV-9 to be avirulent for chickens.
