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Subhajit Biswas

Indian Institute of Chemical Biology CSIR, University of Cambridge, Indian Veterinary Research Institute

ORCID iD 0000-0002-9001-7150
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Major Scientific Breakthroughs and Research Highlights

A. The “Dengue–COVID Conundrum”
Around April 2020, Dr. Biswas noticed that global severity maps of SARS-CoV-2 and dengue seldom overlapped-a finding later confirmed by studies from Brazil. He first demonstrated that pre-pandemic (2017) dengue serum samples cross-reacted in SARS-CoV-2 antibody tests (Journal of Medical Microbiology, 2021), supported by computational modelling (Computational and Structural Biotechnology Journal, 2021) and later validated by studies published from Israel, Taiwan and Brazil. His lab subsequently showed that dengue immunity can, indeed, confer broad-spectrum protection against betacoronaviruses, including SARS-CoV-2, using cell culture and ELISA-based virus neutralization tests (VNTs) (Journal of Medical Virology, 2024). Conversely, highly cross-reactive COVID-19 serum samples (such as Delta wave serums from 2020–21) including majority of samples without prior dengue exposure cross-neutralized dengue virus serotypes 1–4, offering one explanation for the observed global dengue decline during the early pandemic. However, Omicron-wave serums were mostly non-cross-reactive, neutralizing DV-1, -2, -4 but enhancing DV-3 infectivity in vitro by means of ADE-coinciding with rising DV-3 cases during 2022-23 (Journal of Medical Microbiology, 2024). Dr. Biswas coined the term “Dengue–COVID Conundrum” to describe these inverse interactions. His findings have been cited in India’s National Guidelines for Dengue Case Management during COVID-19, NVBDCP guidelines, and Africa CDC’s 2021 COVID-19 Scientific and Public Health Policy Update (please see website https://iicb.res.in/faculty/subhajit-biswas for links).

B. Triple Pathogen Discovery in Kala-azar (Visceral Leishmaniasis)
At CSIR-IICB, Dr. Biswas discovered that most Indian visceral leishmaniasis (VL/kala-azar) samples contained not only the primary causative protozoan Leishmania donovani but also co-infection with Leptomonas seymouri, which itself harboured an RNA virus (Lepsey NLV1)—a “triple pathogen” phenomenon (Archives of Virology, 2017). In 2022, his group demonstrated that the protozoan virus can be detected directly in serum samples of kala-azar patients and is preliminarily linked to reduced IL-18 levels, a cytokine otherwise upregulated during L. donovani infection and critical for parasite clearance (Scientific Reports, 2022). These discoveries opened a new horizon of research towards revisiting the disease pathogenesis and management of kala-azar and its complications, such as Post-Kala-azar Dermal Leishmaniasis (PKDL) and Para-kala-azar dermal leishmaniasis (Para-KDL). In 2024, he has been awarded a 3-year, INR 1.0 crore grant from ICMR to pursue further research in these directions.

C. Discovery of Non-Cytopathic Herpes Simplex Virus (HSV)
Dr. Biswas reported the first global identification of non-cytopathic (non-CPE) herpes simplex virus (HSV) isolates from patients with recurrent herpes infections despite acyclovir therapy. These HSV-1 isolates manifested an unusual characteristic of not being able to show cytopathic effect in permissive cells, with low level of viral protein expressions over several passages. Probably they were evolving towards a more “cryptic” form to establish chronic infection in the host thereby unravelling yet another strategy of HSV to evade the host immune system, besides neuronal latency. This work, featured in Nature India and on Wikipedia, was included in Scientific Reports’ Top 100 Microbiology papers of 2022.

D. Dengue Virus NS1 Mutation Affecting Diagnostics
His team provided the first global evidence that specific NS1 mutations in dengue virus (e.g., Val236➔Ala in DV-2, Trp68➔stop codon in DV-3) can enable the virus to evade NS1 ELISA-based diagnostics (European Journal of Clinical Microbiology & Infectious Diseases, 2022). This discovery has direct societal impact for reducing false-negative dengue diagnoses in clinical settings.

E. Research on herpesvirus Helicase-Primase Inhibitors (HPIs)
During his doctoral & post-doctoral research in Cambridge University, UK, Dr Biswas made significant contribution to characterizing drug-resistant mutations to novel herpesvirus antivirals called HPIs. One such HPI is currently in use in Japan called amenamevir.
He provided a well-defined list of HPI-resistant mutants which are being screened for in humans, in the ongoing drug trials on HPIs globally.
He developed-
(1) New techniques of screening for pre-existing HPI-resistant variant/mutants present in laboratory/ clinical HSV isolates.
(2) Estimated frequency of such mutations in the original virus populations and characterized them in cells & mice.
(3) Discovered novel HPI-resistant mutants like N342K & G352R .
(4) Deduced from the study of HPI-resistant mutants that various HPIs have different "modes of interaction" with the H-P complex & that the HPI, Pritelivir interacts with both helicase and primase to exert its antiviral action.

Employment

  • Indian Institute of Chemical Biology CSIR Senior Principal Scientist
    2024 - Present
  • Indian Institute of Chemical Biology CSIR Principal Scientist
    2018 - 2024
  • Indian Institute of Chemical Biology CSIR Senior Scientist
    2014 - 2018

Education

  • University of Cambridge Ph.D. (Virology); Cambridge Nehru Scholar & ORS Awardee
    2004 - 2008
  • Indian Veterinary Research Institute M.V.Sc. (Gold Medalist)
    2001 - 2003

Projects & Funding

Projects & funding information is unavailable.

Publications (54)