Dr Vinayak Singh

Holistic Drug Discovery and Development Centre

Dr Vinayak Singh

Principal Investigator | Holistic Drug Discovery and Development (H3D) Centre 

The group's primary research focus is on discovering and developing novel therapeutic strategies to combat priority pathogens. This includes:
Mycobacterium tuberculosis: The causative agent of tuberculosis (TB), a major global health threat with millions of cases and deaths annually.
ESKAPE pathogens: A group of six multidrug-resistant bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) posing a significant challenge due to their resistance to many existing antibiotics.

Area of expertise
Drug discovery: Infectious diseases - Tuberculosis and diseases associated with ESKAPE pathogens. Bacteriology: Mycobacterium tuberculosis physiology; Novel drug targets and Drug resistance mechanism(s) in Mycobacterium tuberculosis and ESKAPE pathogens

Group Members
Dr. Mohammad Naiyaz Ahmad (Postdoc)
Thembisa Monki (PhD student)
Ann Ireri (MSc student, Mastercard Foundation Scholar)
Samuel Menbere (MSc student, Mastercard Foundation Scholar)
Igshaan Small (Research Scientist)

Collaborations
International:
Prof. Katarina Mikusova, Comenius University, Slovakia
Prof. Lizbeth Hedstrom, Brandeis University, USA
Prof. Dirk Schnappinger, Weill Cornell Medicine
Prof. Kyu Rhee, Weill Cornell Medicine
Dr. Greg Robertson, Colorado State University
Prof. Tanya Parish, Seattle Children's Hospital
Prof. Stuart J. Conway, UCLA, USA
Prof. Mike Strauss, McGill University, Canada
Prof. Barak Akabayov, Ben-Gurion University of the Negev, Israel
Prof. Tabassum Khan, BNCP, India
Prof. Prashant Kharkar, ICT, India

South Africa:
Prof. Adrian Brink, UCT
Dr. Tashie Makwavarara, Jabu Magagula, Busisiwe Mogodi, Rodney Lucas (UCT-Research Animal Facility)
A/Prof. Suraj Parihar, UCT
Prof. Adrie Steyn, AHRI

Selected recent publications
1. Singh, V.* (2024). Tuberculosis treatment-shortening: Current Progress and Future Outlook. Drug Discovery Today. DOI:10.1016/j.drudis.2024.103955
2. Shyam, M., Kumar, S., Singh, V.* (2024). Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans. ACS Infectious Diseases. 10 (2), 251–269. DOI: 10.1021/acsinfecdis.3c00371
3. Singh, V., Dziwornu, G., Chibale, K. (2023). The implication of Mycobacterium tuberculosis-mediated metabolism of targeted xenobiotics. Nature Reviews Chemistry. 7 (5), 340-354 DOI:10.1038/s41570-023-00472-3.
4. Singh, V., Grzegorzewicz, A. E., Fienberg, S., Müller, R., Khonde, L. P., Sanz, O., Alfonso, S., Urones, B., Drewes, G., Bantscheff, M., Ghidelli-Disse, S., Ioerger, T. R., Angala, B., Liu, J., Lee, R. E., Sacchettini, J. C., Krieger, I. V., Jackson, M., Chibale, K., Ghorpade, S. R. (2022). 1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex in Mycobacterium tuberculosis. ACS Infectious Diseases. 8 (11), 2315-2326. DOI: 10.1021/acsinfecdis.2c00392.
5. Savková, K., Huszár, S., Baráth, P., Pakanová, Z., Kozmon, S., Vancová, M., Tesařová, M., Blaško, J., Kalinak, M., Singh, V., Korduláková, J., Mikušová, K. (2021). An ABC transporter Wzm-Wzt catalyzes translocation of lipid-linked galactan across the plasma membrane in mycobacteria. Proceedings of the National Academy of Sciences (PNAS). 118 (17), e2023663118. DOI: 10.1073/pnas.2023663118
6. de Melo, C.S.*, Singh, V.*, Myrick, A., Simelane, S.B., Taylor, D., Brunschwig, C., Lawrence, N., Schnappinger, D., Engelhart, C.A., Kumar, A., Parish, T., Su, Q., Myers, T.G., Boshoff, H.I.M., Barry, C.E., Sirgel, F.A., Van Helden, P.D., Buchanan, K.I., Bayliss, T., Green, S.R., Ray, P.C., Wyatt, P.G., Basarab, G.S., Eyermann, C.J., Chibale, K., Ghorpade, S.R. (2021). Antitubercular 2-Pyrazolylpyrimidinones: Structure–Activity Relationship and Mode-of-Action Studies. Journal of Medicinal Chemistry. 64, 719-740. DOI:10.1021/acs.jmedchem.0c01727
7. Singh, V., Chibale, K. (2021). Strategies to Combat Multi-Drug Resistance in Tuberculosis. Accounts of Chemical Research, 54, 10, 2361–2376. DOI: 10.1021/acs.accounts.0c00878
8. Singh, V*., Pacitto, A., Donini, S., Ferraris, D.M., Boros, S., Illyés, E., Szokol, B., Rizzi, M., Blundell, T.L., Ascher, D.B., Pato, J., Mizrahi, V. (2019). Synthesis and Structure–Activity Relationship of 1-(5-isoquinolinesulfonyl)piperazine Analogues as Inhibitors of Mycobacterium tuberculosis IMPDH. European Journal of Medicinal Chemistry. 174, 309-329. DOI: 10.1016%2Fj.ejmech.2019.04.027
9. Singh, V., Donini, S., Pacitto, A., Sala, C., Hartkoorn, R., Dhar, N., Keri, G., Ascher, D., Mondésert, G., Vocat, A., Lupien, A., Sommer, R., Buechler, J., Lagrange, S., Warner, D.F., McKinney, J.D., Pato, J., Cole, S.T., Blundell, T., Rizzi, M., Mizrahi, V. (2017). The inosine monophosphate dehydrogenase, GuaB2, is a vulnerable new bactericidal drug target for tuberculosis. ACS Infectious diseases. 3 (1), 5–17. DOI: 10.1021/acsinfecdis.6b00102.
10. Singh, V., Brecik, M., Mukherjee, R., Evans, J.C., Svetlíková, S., Blaško, J., Surade, S., Blackburn, J., Warner, D.F., Mikušová, K. and Mizrahi, V. (2015). The complex mechanism of antimycobacterial action of 5-fluorouracil. Chemistry & Biology. 22 (1), 63-75. DOI: 10.1016/j.chembiol.2014.11.006.