Objective The goal of this randomized placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D 3 [25(OH)D 3 ] in improving vitamin D status in vitamin D deficient/insufficient patients infected with the SARS-CoV-2 (COVID-19) virus. Methods This is a multicenter randomized double blinded randomized placebo-controlled clinical trial. Participants were recruited from three hospitals that are affiliated to [Institution Blinded for Review], and [Institution Blinded for Review]. Results A total 106 hospitalized patients who had a circulating concentration of 25(OH)D <30 ng/ml were enrolled in this study. Within 30 and 60 days 79.4% (26 out of 34) and 100% (24 out of 24) of the patients who received 25(OH)D 3 became sufficient whereas ≤12.5% the patients in the placebo group became sufficient during 2 months follow-up. We observed an overall lower trend for hospitalization, ICU duration, needing ventilator assistance and mortality in the 25(OH)D3 group compared with placebo group but they weren’t statistically significant. Treatment with oral 25(OH)D 3 was associated with a significant increase in the lymphocyte percentage and decrease in the ratio of neutrophils to lymphocytes (NLR) in the patients. The lower NLR was significant associated with reduced ICU admission days and mortality. Conclusion Our analysis indicated that oral 25-hydroxyvitamin D 3 was able to correct vitamin D deficiency/insufficiency in COVID-19 patients that resulted in improved immune function by increasing blood lymphocyte percentage. RCTs with a larger sample size and with higher dose of 25(OH)D3 maybe needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in COVID-19 patients. Ethics and Dissemination The study protocol was approved by the Ethics Committee of [Institution Blinded for Review]. (Approval Number: IR.TUMS.VCR.REC.1399.061). Dissemination plans include academic publications, conference presentations and social media. Trial registration The protocol was registered with the Iranian Registry of Clinical Trials (IRCT) on April 11, 2020 [Number Blinded for Review]. and U.S. National Institutes of Health [Number Blinded for Review] on May 11, 2020.

Persian medicine has recommended clinical experiences and proper herbal remedies for prevention and treatment of microbial infections and respiratory diseases. An open-label, randomized, controlled, multicenter trial was conducted at five hospitals in Tehran and Isfahan provinces of Iran on 358 hospitalized adult patients. A total of 174 patients received standard care and 184 received herbal remedies (polyherbal decoction every 8 hr and two herbal capsules every 12 hr) plus standard care for 7 days. The primary clinical endpoint was the duration of hospital stay, and secondary outcomes were clinical improvement of symptoms based on self-assessment questionnaire. Results demonstrated that these natural decoction and capsules treatment plus routine care significantly decreased duration of hospital dyspnea (3.291 day vs. 6.468 days), accelerated clinical improvement, and decreased symptoms such as dry cough, dyspnea, muscle pain, headache, fatigue, anorexia, chills, runny nose, sputum cough, and vertigo in the treatment group compared with standard-care group.Significant effects of these polyherbal formulations on improving the symptoms of COVID-19 could be incredibly promising for managing this pandemic with acceptable tolerability.

The coronavirus disease-2019 (COVID-19) pandemic started in early 2020 with the outbreak of a highly pathogenic human coronavirus. The world is facing a challenge and there is a pressing need for efficient drugs. Plants and natural compounds are a proven rich resource for new drug discovery. Considering the potential of natural products to manage the pandemic, this article was designed to provide an inclusive map of the stages and pathogenetic mechanisms for effective natural products on COVID-19. New drug discovery for the COVID-19 pandemic can encompass both prevention and disease management strategies. Preventive mechanisms that may be considered include boosting the immune response and hand hygiene in the preexposure phase; and blocking of virus binding and entry in the postexposure phase. Potential therapeutic target mechanisms include virus-directed therapies and host-directed therapies. Several medicinal plants and natural products, such as Withania somnifera (L.) Dunal and propolis for prevention; Tanacetum parthenium (L.) for treatment; and Ammoides verticillata (Desf.) Briq and Nigella sativa L. for both prevention and treatment have been found effective and are good targets for future research. The examples of phytochemical compounds that may be effective include aloin and terpenes as anti-septics; isothymol, dithymoquinone, and glycyrrhizin as inhibitors of virus binding and entry; glycyrrhizin, and berberine as replication suppressants; ginsenoside Rg1 and parthenolide as immunomodulators; and eriocitrin, rhoifolin, hesperidin, naringin, rutin, and veronicastroside as anti-complements. Recognizing different mechanisms of fighting against this virus can lead to a more systematic approach in finding natural products and medicinal plants for COVID-19 prevention and treatment.

Background. Iranian traditional medicine (ITM) is a holistic medical system that uses a wide range of medicinal substances to treat disease. Reorganization and standardization of the data on ITM concepts is a necessity for optimal use of this rich source. In an initial step towards this goal, we created a database of ITM materia medica. Main Body. Primarily based on Makhzan al-Advieh, which is the most recent encyclopedia of materia medica in ITM with the largest number of monographs, a database of natural medicinal substances was created using both text mining methods and manual editing. UNaProd, a Universal Natural Product database for materia medica of ITM, is currently host to 2696 monographs, from herbal to animal to mineral compounds in 16 diverse attributes such as origin and scientific name. Currently, systems biology, and more precisely systems medicine and pharmacology, can be an aid in providing rationalizations for many traditional medicines and elucidating a great deal of knowledge they can offer to guide future research in medicine. Conclusions. A database of materia medica is a stepping stone in creating a systems pharmacology platform of ITM that encompasses the relationships between the drugs, their targets, and diseases. UNaProd is hyperlinked to IrGO and CMAUP databases for Mizaj and molecular features, respectively, and it is freely available at http://jafarilab.com/unaprod/.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterised by airway inflammation and progressive obstruction of the lung airflow. Current pharmacological treatments include bronchodilators, alone or in combination with steroids, or other anti-inflammatory agents, which have only partially contributed to the inhibition of disease progression and mortality. Therefore, further research unravelling the underlying mechanisms is necessary to develop new anti-COPD drugs with both lower toxicity and higher efficacy. Extrinsic signalling pathways play crucial roles in COPD development and exacerbations. In particular, phosphoinositide 3-kinase (PI3K) signalling has recently been shown to be a major driver of the COPD phenotype. Therefore, several small-molecule inhibitors have been identified to block the hyperactivation of this signalling pathway in COPD patients, many of them showing promising outcomes in both preclinical animal models of COPD and human clinical trials. In this review, we discuss the critically important roles played by hyperactivated PI3K signalling in the pathogenesis of COPD. We also critically review current therapeutics based on PI3K inhibition, and provide suggestions focusing on PI3K signalling for the further improvement of the COPD phenotype.