Receptor modification as a therapeutic approach against viral diseases

Poliovirus causes flaccid paralysis through the destruction of motor neurons in the CNS. Susceptibility to its infection is mainly dueto the interaction in between the surface capsid proteins and its receptors on the host cell surface, important for binding,penetration and other necessary events during early infection. Receptor modification is a new approach to treat viral diseases bythe modification of target proteins structure. Binding domains are modified in an effective way to make it difficult for the virus torecognize it. In this study, tolerant and intolerant induced mutations in the poliovirus receptor, VP1 and VP2 were identified andsubstituted in the seed sequence to get the modified versions. Substitutions causing changes in initial folding were short listed andfurther analyzed for high level folding, physiochemical properties and interactions. Highest RMSD values were observed inbetween the seed and the mutant K90F (3.265 Å) and Q130W (3.270Å) respectively. The proposed substitutions were found to havelow functional impact and thus can be further tested and validated by the experimental researchers. Interactions analyses provedmost of the substitutions having decreased affinity for both the VP1 and VP2 and thus are of significant importance againstpoliovirus. This study will play an important role for bridging computational biology to other fields of applied biology and alsowill provide an insight to develop resistance against viral diseases. It is also expected that same approach can also be applicableagainst other viruses like HCV, HIV and other in near future.