Chandipura virus (CHPV), belonging to the Rhabdoviridae family, is an emerging pathogen linked to encephalitis outbreaks, especially in children under 15 years of age. CHPV is primarily spread by sandflies and has led to several outbreaks in India, but CHPV strains from African nations namely Senegal, Kenya and Nigeria are not associated with human infections. This study involved an in-silico analysis aimed at exploring the differences in the G protein between the Indian and African CHPV isolates which would explain the above anomaly. Multiple Sequence Alignment was carried out to identify the amino acid substitution sites between all the Indian and the African CHPV isolates. Additionally, Profile Sequence Alignment (PSA) analysis was also conducted to localize the identified conserved amino acid substitutions between the Indian and the African CHPV G protein, focusing on potential antigenic sites and critical viral domains. Furthermore, an in-silico analysis has been carried out to assess the binding affinity of the CHPV G protein of different countries with the host co-receptor vimentin that is known to be involved in virus entry. Our results indicated that the Indian and the African CHPV G protein sequences exhibited amino acid variations at 19 conserved sites, which were localized within the antigenic sites and other critical viral domains, including the fusogenic site of the CHPV G protein. Furthermore, our analysis predicted significant alterations in either solvent accessibility or torsional angle rotation stemming from the amino acid variations at the aforementioned sites. Additional in-silico analysis also revealed that the Indian CHPV G protein exhibited a markedly superior binding affinity with vimentin compared to its African counterparts. Therefore, the current study provides important findings regarding the variations of the CHPV G protein and highlighting essential amino acid residues that may be targeted for development of future antiviral therapies. • The study examines why Chandipura virus (CHPV) isolates from India exhibit disease symptoms in humans, but their African counterparts do not. In fact, all the CHPV sequences that have been deposited in the Gen bank from Africa so far have been isolated from sandflies. The main conclusions of the research are as follows: • The alignment of CHPV G proteins revealed conserved amino acid differences at 19 distinct sites between the Indian group and the African group (Senegal and Kenya). • In-silico prediction suggests significant structural differences exists between the CHPV G protein of the Indian and African continents. • In-silico prediction showing higher binding affinity of the Indian CHPV G-Protein for Vimentin (binding energy: -650.8 kcal/mol) than Kenya and Senegal (binding energy: - 541.1 & -390 kcal/mol respectively). Vimentin has been earlier experimentally reported as a critical co-receptor for CHPV entry into neuronal cells. • Moreover, Profile Sequence Alignment of India and Kenya CHPV isolates with other rhabdovirus family members aligned the 19 CHPV G protein amino acid substitutions to key antigenic sites and replication associated domains respectively. This amino acid changes within the antigenic sites may aid in the differential immune response of humans towards the CHPV isolates of the two different continents that needs future exploration. • In-silico analysis reveals significant changes in torsional angle rotation and solvent accessibility near the 12 sites of amino acid substitutions.
Jena et al. (Sun,) studied this question.