Abstract: Pharmacological Reports https://doi.org/10.1007/s43440-023-00463-7 SPECIAL ISSUE: REVIEW The Post-COVID Era - Advances and Challenges in Pharmacology Nasal sprays for treating COVID‑19: a scientific note Vivek P. Chavda1 · Kajal P. Baviskar2 · Dixa A. Vaghela3 · Shilpa S. Raut4 · Anjali P. Bedse4 Received: 30 October 2022 / Revised: 6 February 2023 / Accepted: 7 February 2023 © The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences 2023 Abstract Clinical management of COVID-19 has been a daunting task. Due to the lack of specific treatment, vaccines have been regarded as the first line of defence. Innate responses and cell-mediated systemic immunity, including serum antibodies, have been the primary focus of practically all studies of the immune response to COVID-19. However, owing to the difficulties encountered by the conventional route, alternative routes for prophylaxis and therapy became the need of the hour. The first site invaded by SARS-CoV-2 is the upper respiratory tract. Nasal vaccines are already in different stages of development. Apart from prophylactic purposes, mucosal immunity can be exploited for therapeutic purposes too. The nasal route for drug delivery offers many advantages over the conventional route. Besides offering a needle-free delivery, they can be selfadministered. They present less logistical burden as there is no need for refrigeration. The present article focuses on various aspects of nasal spray for eliminating COVID-19. Keywords SARS-CoV-2 · Immunity · Nasal route · Nasal vaccine · Nasal spray · Clinical trials · Devices Abbreviations ACE2 Angiotensin converting enzyme 2 CD4 Clusters of differentiation 4 cGMP Guanosine mono phosphate COVID-19 Coronavirus disease-2019 HCoV Human coronavirus HPMC Hydroxypropyl methyl cellulose IgG Immunoglobulin G IL-2 Interleukin-2 MERS-CoV Middle East respiratory syndrome coronavirus * Vivek P. Chavda vivek.chavda@lmcp.ac.in; Vivek7chavda@gmail.com 1 Department of Pharmaceutics and Pharmaceutical Technology, L M College of Pharmacy, Navrangpura, Ahmedabad, Gujarat 380009, India 2 Department of Pharmaceutical Chemistry, K K Wagh College of Pharmacy, Affiliated to Dr Babasaheb Ambedkar Technological University, Raigad, Lonere, Maharashtra 402103, India 3 Pharmacy Section, L.M. College of Pharmacy, Ahmedabad, Gujarat 380009, India 4 Department of Pharmaceutics, K K Wagh College of Pharmacy, Affiliated to Dr Babasaheb Ambedkar Technological University, Raigad, Lonere, Maharashtra 402103, India mRNA Messenger ribonucleic acid NC Nasal cycle NONS Nitric oxide nasal spray RNA Ribonucleic acid SARS-CoV-2 Severe acute respiratory syndrome coronavirus disease 2 URTI Upper respiratory tract infection