Ritu Goswami

National Institute of Malaria Research

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Amit Raj Sharma

Post Graduate Institute of Medical Education and Research

Amit Sharma

International Centre for Genetic Engineering and Biotechnology

Rini Chaturvedi

All India Institute of Medical Sciences

Jasmita Gill

National Institute of Malaria Research

Anmol Chandele

International Centre for Genetic Engineering and Biotechnology

Sanjeev Kumar

All India Institute of Medical Sciences

Soumyananda Chakraborti

National Institute of Malaria Research

Manju Rahi

Vector Control Research Centre

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International Centre for Genetic Engineering and Biotechnology

National Institute of Malaria Research

All India Institute of Medical Sciences

Academy of Scientific and Innovative Research

Indian Council of Medical Research

Post Graduate Institute of Medical Education and Research

Centro de Ingeniería Genética y Biotecnología

International Centre for Genetic Engineering and Biotechnology

Emory University

All India Institute of Medical Sciences Raipur

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India Needs to Consider Planning a Change to Artemether–Lumefantrine to Treat Plasmodium falciparum Malaria

American Journal of Tropical Medicine and Hygiene (2022)

Manju Rahi Rini Chaturvedi Ritu Goswami Amit Sharma

ABSTRACT. As the malaria elimination target draws closer for India, it must be ensured that the country’s policies, strategies, and tools remain effective. Artemisinin-based combination therapies are the mainstay of Plasmodium falciparum malaria management. India has a differential standard therapy for uncomplicated falciparum malaria in the form of artemether–lumefantrine in its northeastern states and artesunate + sulfadoxine–pyrimethamine in the rest of the country. The clinical failure of artesunate + sulfadoxine–pyrimethamine in the northeast regions was attributed primarily to parasite resistance resulting from mutations in the enzymes dihydropteroate synthase and dihydrofolate reductase. Artemether–lumefantrine was therefore substituted for artesunate + sulfadoxine–pyrimethamine in the region. The change has been a success, as evidenced by the therapeutic efficacy studies conducted at regular intervals in India. However, studies suggest that resistance may be emerging toward sulfadoxine–pyrimethamine in multiple parts of the nation. Hence, there is a possibility that the artesunate + sulfadoxine–pyrimethamine combination may be acting in part as a monotherapy, and this makes the longevity of the artesunate + sulfadoxine–pyrimethamine drug combination therapy uncertain. The increasing presence of drug-resistant mutants in P. falciparum dhps and dhfr genes suggests the need for a policy switch for uncomplicated P. falciparum malaria from artesunate + sulfadoxine–pyrimethamine to artemether–lumefantrine.

Artesunate

Artemether/lumefantrine

Sulfadoxine

Lumefantrine

Sulfadoxine/pyrimethamine

Artemether

DHPS

10.4269/ajtmh.21-1095

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Structural Profiles of SARS-CoV-2 Variants in India

Current Microbiology (2022)

Soumyananda Chakraborti Jasmita Gill Ritu Goswami Sanjeev Kumar Anmol Chandele

India was severely affected by several waves of SARS-CoV-2 infection that occurred during April-June 2021 (second wave) and December 2021-January 2022 (third wave) and thereafter, resulting in >10 million new infections and a significant number of deaths. Global Initiative on Sharing Avian Influenza Data database was used to collect the sequence information of ~10,000 SARS-CoV-2 patients from India and our sequence analysis identified three variants B.1.1.7 (alpha, α), B1.617.2 (delta, Δ), B.1.1.529 (Omicron, Oo) and one Omicron sub-variant BA.2.75 as the primary drivers for SARS-CoV-2 waves in India. Structural visualization and analysis of important mutations of alpha, delta, Omicron and its sub-variants of SARS-CoV-2 Receptor-Binding Domain (RBD) was performed and our analysis clearly shows that mutations occur throughout the RBD, including the RBD surface responsible for human angiotensin-converting enzyme 2 (hACE-2) receptor-binding. A comparison between alpha, delta and omicron variants/sub-variants reveals many omicron mutations in the hACE-2 binding site and several other mutations within 5 Å of this binding region. Further, computational analysis highlights the importance of electrostatic interactions in stabilizing RBD-hACE-2-binding, especially in the omicron variant. Our analysis explores the likely role of key alpha, delta and omicron mutations on binding with hACE-2. Taken together, our study provides novel structural insights into the implications of RBD mutations in alpha, delta and omicron and its sub-variants that were responsible for India's SARS-CoV-2 surge.

10.1007/s00284-022-03094-y

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Citations (11)