Oral and intranasal vaccines against SARS-CoV-2: Current progress, prospects, advantages, and challenges.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a deadly pandemic in the 21st century, resulting in many deaths, economic loss, and international immobility. Vaccination represents the only mechanism to defeat this virus. Several intramuscular vaccines have been approved and are currently used worldwide. MAIN BODY: However, global mass vaccination has not been achieved owing to several limitations, including the need for expertise to administer the injection-based vaccine, improper distribution of the vaccine, and lack of cold chain facilities, particularly in resource-poor, low-income countries. Mucosal vaccines are typically administered either orally or nasally, and several studies have shown promising results for developing these vaccines against SARS-CoV-2 that might serve as viable alternatives to current vaccines. SARS-CoV-2 invades the human body via oral and nasal mucosal surfaces; thus, an oral or nasal vaccine can trigger the immune system to inhibit the virus at the mucosal level, preventing further transmission via a strong mucosal and systematic immune response. Although several approaches toward developing a mucosal vaccine are currently being tested, additional attention is required. CONCLUSION: In this article, the current approaches used to develop effective oral and nasal mucosal vaccines against SARS-CoV-2 and their benefits, prospects, and challenges have been summarized.

A computational comparative analysis of the binding mechanism of molnupiravir's active metabolite to RNA-dependent RNA polymerase of wild-type and Delta subvariant AY.4 of SARS-CoV-2.

The antiviral drug molnupiravir targets the SARS-CoV-2 RNA-dependent RNA polymerase (RdRP) enzyme. Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with COVID-19, according to phase 3 clinical trials. Many mutations have occurred within this virus as a result of its widespread distribution. The current study sought to determine whether mutations in the RdRP of Delta subvariant AY.4 (D-AY.4 RdRP) influence the interaction of the enzyme with molnupiravir triphosphate (MTP), the active metabolite of molnupiravir. The interactions between the wild-type (WT) RdRP and D-AY.4 RdRP with MTP were evaluated based on molecular docking and dynamic simulation (MD) studies. The results show that the MTP interaction is stronger and more stable with D-AY.4 RdRP than with WT RdRP. This study provides insight into the potential significance of administering MTP to patients infected with D-AY.4 RdRP, which may have a more favorable chance of alleviating the illness. According to the findings of this study, MTP has a high likelihood of becoming widely used as an anti-SARS-CoV-2 agent. The fact that MTP is not only cytotoxic but also mutagenic to mammalian cells, as well as the possibility that it may cause DNA damage in the host, have all been raised as potential concerns.