A Review on Immunological Responses to SARS-CoV-2 and Various COVID-19 Vaccine Regimens.

The transmission of SARS-CoV-2 has caused serious health crises globally. So far, 7 vaccines that are already being assessed in Phase IV clinical trials are, Comirnaty/ Pfizer; Spikevax/Moderna (m RNA vaccine); Vaxzevria or Covishield; Ad26.COV2.S; Ad5-nCoV (adenoviral vector-based vaccine); CoronaVac and BBIBP-CorV (inactivated virus vaccine). Besides, there are about 280 vaccines that are undergoing preclinical and clinical trials including Sputnik-V, Covaxin or BBV152, and NVX-CoV2373. These vaccines are being studied for their immunological responses and efficiency against COVID-19, and have been reported to demonstrate effective T and B cell responses. However, the long-lasting immunity of these vaccine regimens still needs to be investigated. An in-depth understanding of the vaccine efficacy and immune control mechanism is imperative for the rational purposing and implementation of the vaccines. Hence, in this review, we have comprehensively discussed the immune response induced in COVID-19 patients, as well as in the convalescent individuals to avoid reinfection. Moreover, we have also summarized the immunological responses and prophylactic efficacy of various COVID-19 vaccine regimens. In this context, this review can give insights into the development of effective vaccines against SARS-CoV-2 and its variants in the future.

Evaluation of the target-specific therapeutic potential of herbal compounds for the treatment of cancer.

Cancer is among one of the most fatal diseases leading to millions of death around the globe. Chemotherapy is the most popular conventional approach for the treatment of cancer. However, this is usually associated with various side effects and puts the patients under extreme physical and mental stress. Besides, there are increasing concerns about drug resistance. Thus, to surmount these limitations, there is a need to explore some alternative treatments. Studies related to plant-derived compounds are crucial in the search for safer and more efficient treatments. Plants and their associated secondary metabolites have been a revolutionary approach in the field of cancer treatment, as they give answers to almost all the constraints faced by synthetic drugs. Various plants and associated secondary metabolites display a great prospective as cytotoxic anticancer agents due to their specific interference with validated drug targets, such as inhibitors of mitosis, topoisomerase I and II inhibitor, DNA interactive agent, protein kinase inhibitors, inhibitors of DNA synthesis. In this review, the therapeutic potential of various natural compounds and their derivatives are presented based on their molecular targets. These herbal compounds and their derivatives could provide a rich resource for novel anticancer drug development.

Identification of novel inhibitors of angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19).

The pandemic outbreak of coronavirus (SARS-CoV-2) is rapidly spreading across the globe, so the development of anti-SARS-CoV-2 agents is urgently needed. Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). The molecular docking was applied to dock a set of representative compounds within the active site region of target receptor protein using 0.8 version of the PyRx virtual screen tool and analyzed by using discovery studio visualizer. Based on the highest binding affinity, 23 compounds were shortlisted as a lead molecule using molecular docking analysis. Among them, ß-sitosterol was found with the highest binding affinity - 12.2 kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor. Similarly, luteoxanthin and violaxanthin followed by rutin also displayed stronger binding efficiency. We propose these compounds as potential lead candidates for the development of target-specific therapeutic drugs against COVID-19.

Role of Cytochrome P450 3A4 in Cancer Drug Resistance: Challenges and Opportunities.

One of the biggest obstacles to the treatment of diseases, particularly serious conditions like cancer, is therapeutic resistance. The process of drug resistance is influenced by a number of important variables, including MDR genes, drug efflux, low-quality medications, inadequate dosage, etc. Drug resistance must be addressed, and new combinations based on the pharmacokinetics/pharmacodynamics (PK-PD) characteristics of the partner pharmaceuticals must be developed in order to extend the half-lives of already available medications. The primary mechanism of drug elimination is hepatic biotransformation of medicines by cytochrome P450 (CYP) enzymes; of these CYPs, CYP3A4 makes up 30-40% of all known cytochromes that metabolize medications. Induction or inhibition of CYP3A4-mediated metabolism affects the pharmacokinetics of most anticancer drugs, but these details are not fully understood and highlighted because of the complexity of tumor microenvironments and various influencing patient related factors. The involvement of CYPs, particularly CYP3A4 and other drug-metabolizing enzymes, in cancer medication resistance will be covered in the current review.

Identification of novel inhibitors from Urtica spp against TNBC targeting JAK2 receptor for breast cancer therapy.

Breast cancer is the most prevalent form of cancer in women globally, and TNBC (triple-negative breast cancer) is its aggressive type since it lacks the usual targets. JAK2/STAT3 pathway can be an important lead in anticancer drug discovery, as restraining the downstream signalling of this pathway results in the induction of cell apoptosis. Moreover, various limitations associated with chemotherapy are the reason to find an alternative herbal-based therapy. For this study, we collected Urtica dioica and U. parviflora from different regions of Uttarakhand, followed by preparation of their leaf and stem extracts in different solvents. The GC-MS analysis of these extracts revealed a total of 175 compounds to be present in them. Further, by molecular docking approach, we studied the interaction between these compounds and JAK2, and 12 major compounds with better binding energy than the control Paclitaxel were identified. In addition, the selected hits were also reported to display better pharmacokinetic properties. Moreover, extracts from both the Urtica spp. displayed significant anticancer activity against MDA-MB-231(TNBC cell line) and exhibited lower cytotoxicity in healthy cell lines, i.e. HEK293T, indicating that these extracts were safer to use. Hence, the findings in our study can be crucial in the area of herbal-based target-specific drug development against breast cancer.

Evaluation of target-specific natural compounds for drug discovery against Leishmaniasis.

Leishmaniasis is a parasitic disease with no effective vaccine still now. Globally, it has affected millions of people, precisely in the undeveloped and developing countries. The control strategy for leishmaniasis depends only on chemotherapeutic methods that are associated with several side effects. Therefore, to overcome these negative impacts natural products are the best alternative for developing effective herbal-based drugs, which can act as one of the safest and effective alternative options to treat this particular disease. Leishmania, the causative agent of this disease possesses unique enzymes and metabolic pathways that are different from its mammalian host. Moreover, these unique enzymes, along with the signaling molecules and metabolic pathways that are crucial for its survival, serve as a suitable drug target for the evaluation of specific natural inhibitors to overcome leishmaniasis. Hence, in this review, we have discussed various specific targets of Leishmania, along with their natural inhibitors which can play a significant role in anti-leishmanial drug discovery.

Vaccination strategies to combat novel corona virus SARS-CoV-2.

The 2019-novel coronavirus disease (COVID-19) is caused by SARS-CoV-2 is transmitted from human to human has recently reported in China. Now COVID-19 has been spread all over the world and declared epidemics by WHO. It has caused a Public Health Emergency of International Concern. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Due to the rapid increase of SARS-CoV-2 infections and unavailability of antiviral therapeutic agents, developing an effective SAR-CoV-2 vaccine is urgently required. SARS-CoV-2 which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. In this review we have summarized various vaccine candidates i.e., nucleotide, subunit and vector based as well as attenuated and inactivated forms, which have already been demonstrated their prophylactic efficacy against MERS-CoV and SARS-CoV, so these candidates could be used as a potential tool for the development of a safe and effective vaccine against SARS-CoV-2.