Debananda Das, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 10 - Magnuson Clinical Center, Room 5A11
- Bethesda, MD 20892-1868
Dr. Das's current research interests are as follows: 1) Discovery and optimization of small molecule inhibitors against SARS-CoV-2. 2) Determining the (structural) mechanism of resistance of HIV against protease and reverse transcriptase inhibitors. 3) Structural interactions of nucleoside reverse transcriptase inhibitors against Hepatitis-B virus (HBV) and 4) virtual screening to identify new classes of inhibitors against HIV.
Areas of Expertise
1) anti-HIV inhibitors 2) anti-SARS-CoV-2 inhibitors 3) structure-based discovery and design of small molecule inhibitors 4) virtual screening for small molecule lead identification 5) structure to function relationships 6) computational structural biology and computational chemistry.
Dr. Das' current research interests are as follows:
1. Virtual screening to identify small molecules that bind to SARS-CoV-2 proteases and exert antiviral activity. We carry out a virtual screen that combines the concept of shape similarity of small molecules with their structural interactions with SARS-CoV-2 proteases. SARS-CoV-2 encodes two distinct proteases for proteolytic processing. One is a papain-like cysteine protease (PLpro) and the second is a chymotrypsin-like cysteine protease (3CLpro or Mpro). Inhibition of either protease function by small molecule inhibitors also inhibits viral replication. Our aim is to discover novel scaffolds that bind to PLpro and 3CLpro by virtual screening. We use a combination of enzyme kinetics, x-ray crystallography and molecular dynamics simulations to unambiguously characterize the mechanism of binding.
2. Mechanism of resistance of HIV against protease inhibitors. We use x-ray crystallography and molecular simulations to determine the structural changes that contribute to drug resistance against HIV. The research helps in designing newer generation of inhibitors with improved potency and resistance profile.
A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication
Identification of a novel long-acting 4’-modified nucleoside reverse transcriptase inhibitor against HBV
Activity and structural analysis of GRL-117C: a novel small molecule CCR5 inhibitor active against R5-tropic HIV-1s
Insights into the Mechanism of Inhibition of CXCR4: Identification of Piperidinylethanamine Analogs as Anti-HIV-1 Inhibitors
Debananda Das, Ph.D.
Dr. Das has a M.S. in chemistry from the Indian Institute of Technology, Kanpur, a M.Tech. in chemical analysis from the Indian Institute of Technology, Delhi, and a Ph.D. in chemistry from the University of New Orleans (Advisor: Prof. Scott Whittenburg). His postdoctoral research was on QM/MM methods and applications in the group of Dr. Bernard Brooks at NHLBI/NIH. He worked for Tripos, Inc. before joining the HIV & AIDS Malignancy Branch (HAMB) at NCI in 2005. At HAMB, he works in a multi-disciplinary environment focusing on the design, synthesis, and development of the next-generation of therapeutic agents against HIV, and on the structure to function relationships of reverse transcriptase inhibitors of the Hepatitis-B virus. Since the beginning of the SARS-CoV-2 pandemic, he has worked on the structural interactions of protease inhibitors targeting the main protease of SARS-CoV-2.