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 were 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.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00284-022-03094-y.