Current Pharmaceutical Design - Volume 27, Issue 13, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to severe disease in some cases, leading to acute respiratory distress syndrome, multi-organ failure, and death. This severe phenotype seems to be associated with a cytokine storm and immune dysregulation. Increased pro-inflammatory cytokines and CD14⁺CD16⁺ inflammatory monocytes, lymphopenia, and decreased levels of regulatory T cells are some of the immunological features that are seen in patients with SARS-CoV-2. As the outcome of SARS-CoV-2 is influenced by both viral virulence and dysregulated inflammatory response, a combination therapy approach using antiviral drugs plus anti-inflammatory treatments, such as corticosteroids, monoclonal antibodies against the IL-6 and IL-1β pathways, and JAK inhibitors are under clinical trials.

For nearly two decades, coronaviruses have caused many health and economic problems, while no effective commercial vaccine has yet been developed. It is worth mentioning that despite some mutations and recombination in SARS-CoV-2, its genotype is very close to the original strain from Wuhan, China. Therefore, the development of an effective vaccine would be promising. It might be hypothesized that BCG vaccination is performed in high-risk populations before the commercialization of an effective SARS-CoV-2 vaccine. However, the development of an effective vaccine without considering the adverse immune reactions derived from antibody-dependent or cell-based immune enhancement may threaten vaccinated people's lives and long-term side effects must be considered. To this end, targeting of the receptor-binding domain (RBD) in spike and not whole spike, glycolization of FC receptors, PD-1 blockers, CPPs, etc., are promising. Therefore, the subunit vaccines or RNA vaccines that encode the RBP segment of the spike are of interest. To enhance the vaccine efficacy, its co-delivery with an adjuvant has been recommended. Nanoparticles modulate immune response with higher efficiency than the soluble form of antigens and can be functionalized with the positively charged moieties and ligands of targeted cells, such as dendritic cells, to increase cellular uptake of the antigens and their presentation on the surface of immune cells. This research aimed to discuss the COVID-19 vaccines entering the clinical trial and their mode of action effective immunity against the virus and discusses their advantages compared to each other.

Cannabis sativa is a well-known plant that has been recognized for its benefits since ancient times by several medicinal systems, including those of China, India, Greece, and Egypt. Although C. sativa is one of the most investigated medicinal plants in the world, it faces some of the greatest controversies surrounding its legalization and use as a medication. C. sativa contains several hundred phytoconstituents, including the infamous “cannabinoids”. It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where cannabis is still facing legal obstacles. The current review focuses on the most recent literature pertaining to various applications of cannabinoids, with a special focus on the medicinal aspect of these phytochemicals. Peer-reviewed articles focusing on the importance of cannabis and cannabinoids are the target of this review. Articles were selected based on the relevance to the general scope of the work, i.e., application of cannabinoids. Cannabinoids can truly be regarded as wonder drugs, considering their immense diversity of usage. Unfortunately, however, many of the mares have never been researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizon for the use of these natural drugs in medicines such as Epidiolex® (cannabidiol, used for the treatment of severe forms of epilepsy) and Sativex®(Δ⁹-tetrahydrocannabinol and cannabidiol, used for the treatment of spasticity caused by multiple sclerosis). Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9-tetrahydrocannabinol (Δ⁹-THC), a psychoactive component. This review addresses the most important applications or current utilization of cannabinoids in a variety of treatments such as chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicable diseases, glaucoma, and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, cannabis has a myriad of bioactive compounds that have the potential to increase the list of approved cannabinoids suitable for therapy.

Background: The coronavirus disease 2019 (COVID-19) pandemic has changed the global scenario. To date, there are no treatment or preventive options. The discovery of a new drug will take time. In addition, the new drug will have side effects, and the virus will gradually become resistant to it. Therefore, it is important to search for a drug with a natural origin. Objective: In this review, we analyzed and summarized various ethnomedicinal plants and their bioactive compounds as a source of antiviral agents for COVID-19 prevention and treatment. Methods: From the literature, we selected different natural compounds that can act as potential targets at low cost with broad-spectrum antiviral activity. Results: Of the 200 Chinese herbal extracts tested for their possible role against SARS-CoV, Lycoris radiata, Artemisia annua, Pyrrosia lingua, and Lindera aggregate showed anti-SARS-CoV effects with the median effective concentration = 2.4-88.2 μg/mL. Conclusion: Ethnomedicinal herbs can be used as an alternative source of novel, promising antiviral agents that might directly or indirectly inhibit the COVID-19 progression.

One of the biggest challenges of public health worldwide is reducing the number of events and deaths related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The angiotensinconverting enzyme 2 (ACE-2), a carboxypeptidase that degrades angiotensin II into angiotensin 1-7, has been identified as a potent receptor for SARS-CoV-2. In the last decades, ACE inhibition has assumed a central role in reducing cardiovascular and renal events. However, with the advent of COVID-19, attention has been turned to ACE-2 as a possible target to reduce virus binding to different human cells. This review aims to discuss recent developments related to the medicinal properties of natural compounds as ACE/ACE-2 inhibitors, which should be highlighted in the future development of studies looking for modulators in SARS-CoV-2 infection. Data show that bioactive compounds isolated from several natural products act by inhibiting ACE/ACE-2, which changes the entire axis of this system. Of the compounds addressed in this review, 7 phenolic compounds, including quercetin, curcumin, naringenin, luteolin, hesperidin, mangiferin, and gallic acid showed binding affinity with molecular ACE-2 target in silico, and 1, esculetin, decreased ACE-2 expression in vivo. Regarding terpenoids and alkaloids, nimbin, withaferin A, andrographolide, zingiberene and, berberine, piperine and thebaine, respectively, showed a binding affinity with molecular ACE-2 target in silico. These findings reinforce the need for future preclinical and clinical studies on these compounds and specific inhibitory effects on ACE-2 of all the other compounds described herein only as nonspecific ACE inhibitors. It is important to mention that some natural compounds such as magnolol, resveratrol, rosmarinic acid, tanshinone IIA, and nicotine have also demonstrated the potential to increase the activity or expression of ACE-2, and could therefore aggravate SARS-CoV-2 infection.

Tocilizumab is a humanised interleukin-6 receptor-inhibiting monoclonal antibody that is currently approved for the treatment of rheumatoid arthritis and other immune-related conditions. Recently, tocilizumab has been investigated as a possible treatment for severe coronavirus-induced disease 2019 (COVID-19). Despite the lack of direct antiviral effects, tocilizumab could reduce the immune-induced organ damage caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infection. Until recently, most reports on tocilizumab for COVID-19 included a limited number of patients, preventing an overall evaluation of its efficacy and safety for this specific condition. Therefore, we reviewed the literature regarding the physiopathological rationale of tocilizumab for COVID-19 and its outcomes. We searched the MEDLINE database with the string “(SARS-CoV-2 OR coronavirus OR COVID-19 OR MERS- cov OR SARS-cov) AND (IL-6 OR interleukin 6 OR tocilizumab)”. While the scientific rationale supporting tocilizumab for COVID-19 is solid, the evidence regarding the outcomes remains controversial. Available data and results from ongoing trials will provide useful information in the event of new COVID-19 outbreaks or future pandemics from different coronaviruses.

Over 57 million people have been confirmed to have coronavirus disease 2019 (COVID-19) worldwide. Although several drugs have shown potential therapeutic effects, there is no specific drug against COVID-19. In this review, we summarized potential therapeutic agents against COVID-19 with clinical evidence, including antiviral agents, anti-cytokine storm syndrome agents, and vaccines, as well as other drugs. In addition, we briefly discussed their effects on COVID-19, which will contribute to developing treatment plans.

The spread of a new strain of coronavirus, SARS-CoV-2, a pandemic, poses a serious health problem for all humanity. Compared with the previous outbreaks of coronavirus infection in 2002 and 2012, COVID-19 infection has high rates of lethality, contagiousness, and comorbidity. The effective methods of prevention and treatment are extremely limited. Oxidative stress is actively involved in the mechanisms of initiation and maintenance of violations of homeostatic reactions in respiratory viral infections. It is important to stop systemic inflammation aimed at "extinguishing" the cytokine "storm", caused by the production of reactive oxygen species. Antioxidant defense medications, such as vitamin C, N-acetylcysteine, melatonin, quercetin, glutathione, astaxanthin, polyphenols, fat-soluble vitamins, and polyunsaturated fatty acids have proven well in experimental and clinical studies of influenza, pneumonia, and other respiratory disorders. The use of medications with antioxidant activity could be justified and most probably would increase the effectiveness of the fight against new coronavirus.

Introduction: The rapid emergence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-- CoV-2) has resulted in an increased mortality rate across the globe. However, the underlying mechanism of SARS-CoV-2 altering human immune response is still elusive. The existing literature on miRNA mediated pathogenesis of RNA virus viz. Dengue virus, West Nile virus, etc. raises a suspicion that miRNA encoded by SARS-CoV-2 might facilitate virus replication and regulate the host’s gene expression at the post-transcriptional level. Methods: We investigated this possibility via computational prediction of putative miRNAs encoded by the SARS-CoV-2 genome using a novel systematic pipeline that predicts putative mature-miRNA and their targeted genes transcripts. To trace down if viral-miRNAs targeted the genes critical to the immune pathway, we assessed whether mature miRNA transcripts exhibit effective hybridization with the 3’UTR region of human gene transcripts. Conversely, we also tried to study human miRNA-mediated viral gene regulation to get insight into the miRNA mediated offense and defense mechanism of virus and its host organisms in toto. Results: Our analysis led us to shortlist six putative miRNAs that target, majorly, genes related to cell proliferation/ differentiation/signaling, and senescence. Nonetheless, they also target immune-related genes that directly/ indirectly orchestrate immune pathways like TNF (Tumor Necrosis Factor) signaling and Chemokine signaling pathways putatively serving as the nucleus to cytokine storms. Conclusion: Besides, these six miRNAs were found to be conserved so far across 80 complete genomes of SARS-CoV-2 (NCBI Virus, last assessed 12 April 2020) including Indian strains that are also targeted by 7 human miRNAs and can, therefore, be exploited to develop MicroRNA-Attenuated Vaccines.

Background: This study is an original contribution to the gender-based perspective of measuring knowledge and practice towards COVID-19 among the Saudi population. Objective: This study investigates the existing knowledge of COVID-19 among both genders and its likely use in practice to combat COVID-19. Design and Setting: Cross-sectional study with an online survey and data collected from all the five regions of Saudi Arabia. Participants and Methods: A structured, self-reported validated questionnaire was developed based on the World Health Organization (WHO) general public advice towards COVID-19 prevention. This study has employed snow-ball sampling technique. Sample Size: 627 participants (Male n=343, 54.7%) and (Females n=284, 45.3%). Results: This study has found that women not only carry better knowledge, but their practicing behavior is far better than the male respondents. Females practiced their knowledge of hands hygiene more in comparison to males (86% vs. 80 %, p >0.05). Female respondents were also practicing more about sneezing/coughing into their elbows as compared to males (79% vs. 71%, p < 0.05). Likewise, the practice of knowledge of staying at home to prevent infection (females 98.2% vs males 95.5%, p > 0.05), and (females 83.2% vs. males 81.5%, p > 0.05), respectively. Conclusion: This study shows that women were more compliant with the WHO public health COVID-19 prevention advice than men, which can decrease the chances of COVID-19 infection.