Ruchika Bhat

Bio: Ruchika Bhat is an academic researcher from Indian Institute of Technology Delhi. The author has contributed to research in topics: Hepatitis B virus & Medicine. The author has an hindex of 4, co-authored 10 publications receiving 30 citations. Previous affiliations of Ruchika Bhat include Indian Institutes of Technology.

Improving the binding affinity estimations of protein–ligand complexes using machine-learning facilitated force field method

Abstract: Scoring functions are routinely deployed in structure-based drug design to quantify the potential for protein–ligand (PL) complex formation. Here, we present a new scoring function Bappl+ that is designed to predict the binding affinities of non-metallo and metallo PL complexes. Bappl+ outperforms other state-of-the-art scoring functions, achieving a high Pearson correlation coefficient of up to ~ 0.76 with low standard deviations. The biggest contributors to the increased performance are the use of a machine-learning model and the enlarged training dataset. We have also evaluated the performance of Bappl+ on target-specific proteins, which highlighted the limitations of our function and provides a way for further improvements. We believe that Bappl+ methodology could prove valuable in ranking candidate molecules against a target metallo or non-metallo protein by reliably predicting their binding affinities, thus helping in the drug discovery process.

Toward development of generic inhibitors against the 3C proteases of picornaviruses.

Abstract: Development of novel antivirals, which requires knowledge of the viral life cycle in molecular detail, is a daunting task, involving extensive investments, and frequently resulting in failure. As there exist significant commonalities among virus families in the manner of host interaction, identifying and targeting common rather than specific features may lead to the development of broadly useful antivirals. Here, we have targeted the 3C protease of Hepatitis A Virus (HAV), a feco-orally transmitted virus of the family Picornaviridae, for identification of potential antivirals. The 3C protease is a viable drug target as it is required by HAV, as well as by other picornaviruses, for post-translational proteolysis of viral polyproteins and for inhibiting host innate immune pathways. Computational screening, followed by chemical synthesis and experimental validation resulted in identification of a few compounds which, at low micromolar concentrations, could inhibit HAV 3C activity. These compounds were further tested experimentally against the 3C protease of Human Rhinovirus, another member of the Picornaviridae family, with comparable results. Computational studies on 3C proteases from other members of the picornavirus family have indicated that the compounds identified could potentially be generic inhibitors for picornavirus 3C proteases.

Discovery of small molecule inhibitors of chikungunya virus proteins (nsP2 and E1) using in silico approaches.

Abstract: Chikungunya virus (CHIKV) has emerged as a major viral threat, affecting over a million people worldwide per year. It is a vector borne disease transmitted to the human by Ades mosquitoes and prima...

Epidemiology and molecular characterization of chikungunya virus from human cases in North India, 2016.

Abstract: Chikungunya virus (CHIKV), an arthropod-borne Alphavirus is responsible for chikungunya disease. Arthralgia and arthritis are the major symptom. Some patients recover early while others for a very long time. This study provides, epidemiology and molecular characterization of three whole-genome sequences of CHIKV and assessed phylogenetic analysis, physiological properties, antigenicity, and B-cell epitope prediction by in silico. We report the clinical epidemiology of 325 suspected patients. Of these, 118 (36.30%) were confirmed CHIKV positive by either PCR or ELISA. Clinical analysis showed joint pain, joint swelling and headache were frequent and significant features. Phylogenie analysis showed the currently circulating strain is in close clustring to Africa, Uganda, and Singapore CHIKV strains. Molecular characterization by WGS was done. Thirty eight amino acid changes in the nonstructural proteins were found with respect to the S27 (ECSA) strain. Of these five located in nsP2. Similarly, 34 amino acid changes in structural proteins were observed. The major change was notice; in E3 protein hydropathicity -0.281 to -0.362, in E2 isoelectric point (pI) 8.24 to 8.37, instability index 66.08 to 71.062, aliphatic index varied from 74.69 to 68.59 and E3 75.79 to 70.05. In nsP1 protein pI varies from 6.62 to 8.04, while no other change was observed in structural and nonstructural protein. The linear B-cell epitopes, position, and number varied with the mutation. The molecular characterizations of WGS demonstrate the observation of protein, antigenicity with respect to the mutation.

Antivirals against the Chikungunya Virus.

Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. As many patients develop a painful chronic stage and neither antiviral drugs nor vaccines are available, the development of a potent CHIKV inhibiting drug is crucial for CHIKF treatment. A comprehensive summary of current antiviral research and development of small-molecule inhibitor against CHIKV is presented in this review. We highlight different approaches used for the identification of such compounds and further discuss the identification and application of promising viral and host targets.

Antiviral therapeutics for chikungunya virus

Abstract: Introduction: Chikungunya virus (CHIKV), a reemerging human arthropod borne virus, can causes global epidemic outbreaks and has become a serious health concern due to the unavailability of any antiviral therapy/vaccine. Extensive research has been conducted to target different proteins from CHIKV to curtail the spread of virus.Areas covered: This review provides an overview of the granted patents including the current status of antiviral strategies targeting CHIKV.Expert opinion: Under the current scenario, potential molecules and different approaches have been utilized to suppress CHIKV infection. MV-CHIKV and VRC-CHKVLP059-00-VP vaccine candidates have successfully completed phase I clinical trials and ribavirin (inhibitor) has shown significant inhibition of CHIKV replication and could be the most promising candidates. The drug resistance and toxicity can be modulated by using the inhibitors/drugs in combination. Moreover, nanoparticle formulations can improve the efficacy and bioavailability of drugs.

Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection.

Abstract: Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis, and this infection occasionally causes acute liver failure. HAV infection is associated with HAV-contaminated food and water as well as sexual transmission among men who have sex with men. Although an HAV vaccine has been developed, outbreaks of hepatitis A and life-threatening severe HAV infections are still observed worldwide. Therefore, an improved HAV vaccine and anti-HAV drugs for severe hepatitis A should be developed. Here, we reviewed cell culture systems for HAV infection, and other issues. This review may help with improving the HAV vaccine and developing anti-HAV drugs.