Computational Workflow to Design Novel Vaccine Candidates and Small-Molecule Therapeutics for Schistosomiasis
Emmanuel Oluwadare Balogun,
Gideon Ibrahim Joseph,
Samuel Charles Olabode,
Naziru Abdulkadir Dayaso,
Ammar Usman Danazumi,
Rachael Bashford-Rogers,
James H. Mckerrow,
Ghulam Jeelani,
Conor R. Caffrey
Affiliations
Emmanuel Oluwadare Balogun
Department of Biochemistry, Ahmadu Bello University, Zaria 810001, Kaduna, Nigeria
Gideon Ibrahim Joseph
Department of Biochemistry, Federal University of Technology, Minna PMB 65, Niger, Nigeria
Samuel Charles Olabode
Department of Biochemistry, Ahmadu Bello University, Zaria 810001, Kaduna, Nigeria
Naziru Abdulkadir Dayaso
Department of Biochemistry, Ahmadu Bello University, Zaria 810001, Kaduna, Nigeria
Ammar Usman Danazumi
Department of Biochemistry, Ahmadu Bello University, Zaria 810001, Kaduna, Nigeria
Rachael Bashford-Rogers
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
James H. Mckerrow
Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, MC0657, La Jolla, CA 92093, USA
Ghulam Jeelani
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Conor R. Caffrey
Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, MC0657, La Jolla, CA 92093, USA
Human schistosomiasis, caused by the Schistosoma trematode, is a neglected parasitic disease affecting over 250 million people worldwide. There is no vaccine, and the single available drug is threatened by drug resistance. This study presents a computational approach to designing multiepitope vaccines (MEVs) targeting the cercarial (CMEV) and schistosomular (SMEV) stages of schistosomes, and identifies potential schistosomicidal compounds from the Medicine for Malaria Ventures (MMV) and SuperNatural Database (SND) libraries. The designed vaccines (CMEV and SMEV) are engineered to provoke robust immune responses by incorporating a blend of T- and B-cell epitopes. Structural and immunoinformatics evaluations predicted robust interactions of CMEV and SMEV with key immune receptors and prolonged immune responses. In addition, molecular docking identified several compounds from the MMV and SND libraries with strong binding affinities to vital Schistosoma cathepsin proteases, indicating their potential as schistosomicidal agents. Our findings contribute to the potential development of effective vaccines and drugs against schistosomiasis.
