Desigan Kumaran
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Desigan Kumaran has a total of 18 co-authors. Here are the top co-authors by number of shared publications:
- Babak Andi
Center for BioMolecular Structure, National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, USA
2 shared publications - Sean McSweeney
National Synchrotron Light Source II Brookhaven National Laboratory 11973 Upton NY US
2 shared publications Alexei S. Soares
Center for BioMolecular Structure, NSLS-II, Brookhaven National Laboratory, Upton, USA
1 shared publication- Ali Ebrahim
Structural Biology Initiative, CUNY Advanced Science Research Center
1 shared publication - Blake Theodore Riley
Structural Biology Initiative CUNY Advanced Science Research Center New York New York USA
1 shared publication Dale F. Kreitler
Center for BioMolecular Structure, NSLS-II, Brookhaven National Laboratory, Upton, USA
1 shared publication
Latest Publications
- Open Access
- 17 August 2022
- Published by International Union of Crystallography (IUCr) in IUCrJ
- Vol. 9 (5) , 682-694
The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)
The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for the development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these data sets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a perturbation-dependent conformational landscape for Mpro, including a mobile zinc ion interleaved between the catalytic dyad, mercurial conformational heterogeneity at various sites including a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to aid preparation for future coronavirus pandemics.
- 17 August 2022
- Published by International Union of Crystallography (IUCr) in IUCrJ
- Vol. 9 (5) , 682-694
Open AccessThe temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)
The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for the development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these data sets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a perturbation-dependent conformational landscape for Mpro, including a mobile zinc ion interleaved between the catalytic dyad, mercurial conformational heterogeneity at various sites including a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to aid preparation for future coronavirus pandemics.
- Open Access
- 16 July 2022
- Published by Springer Nature in Scientific Reports
- Vol. 12 (1) , 1-12
Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main protease (Mproalso known as 3CLpro) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the MproCys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the Mproas potential COVID-19 therapeutics for further testing and possibly clinical trials.
- 16 July 2022
- Published by Springer Nature in Scientific Reports
- Vol. 12 (1) , 1-12
Open AccessHepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main protease (Mproalso known as 3CLpro) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the MproCys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the Mproas potential COVID-19 therapeutics for further testing and possibly clinical trials.