Disulfiram: A repurposed drug in preclinical and clinical development for the treatment of infectious diseases

This article reviews preclinical and clinical studies on the repurposed use of disulfiram (Antabuse) as an antimicrobial agent. Preclinical research covered on the alcohol sobriety aid include uses as an anti-MRSA agent, a carbapenamase inhibitor, antifungal drug for candidiasis, and a treatment for parasitic diseases due to protozoa (e.g., giardiasis, leishmaniasis, malaria) and helminthes (e.g., schistosomiasis, trichuriasis). Past, current, and pending clinical studies on disulfiram as a post-Lyme disease syndrome (PTLDS) therapy, an HIV latency reversal agent, and an intervention for COVID-19 infections are also reviewed.

Use of the genus Satureja as food supplement: possible modulation of the immune system via intestinal microbiota during SARS-CoV-2 infection?

Satureja genus belongs to the Lamiaceae family, they are used in food products and by pharmaceutical and cosmetic industries. The chemical composition of Satureja are responsible for its pharmacological and phytochemical properties. Among the various biological activities, notably antioxidant, antibacterial and antifungal, Satureja also has a potential antiviral activity. The existence of a microbiota modulation potential by Satureja in farming animals has also been reported. Viral pathologies are one of the main causes of disease in the world. It is commonly known that gut microbiota plays a crucial role in the fight and progression of viral infection. Previous studies conducted on coronavirus disease 2019 (COVID-19) pandemic have prouved an imbalance in the intestinal and pulmonary microbiota via gut-lung axis. Knowing the properties of Satureja and its traditional use, one can suggest the possibility of using it as dietary supplement to modulate immune system in order to prevent and fight viral infections. The objective of this review is to reveal the potential impact of medicinal plants such as Satureja genus as food supplement, on immune enhancing during SARS-CoV-2 infection and their relationships with the intestinal microbiota.

In silico drug repurposing for the identification of antimalarial drugs as candidate inhibitors of SARS-CoV-2

: Coronavirus disease (COVID-19) is a severe acute respiratory condition that affected millions of populations worldwide in early 2020, indicating for a global health emergency.As regards the deteriorating trends in COVID-19, none of the drugs were confirmed to have substantial efficacy in the potential treatment of COVID-19 patients in large-scale trials.The purpose of this research was to identify potential antimalarial candidate molecules for the treatment of COVID and to evaluate the possible mechanism of action by in silico screening method. Insilicoscreening study of various antimalarial compounds like Amodiaquine, Chloroquine, Hydroxychloroquine, Mefloquine, Primaquine, and Atovaquone were conducted with PyRx and AutoDoc 1.5.6 tools on ACE 2 receptor, 3CL protease, Hemagglutinin esterase, Spike protein SARS HR1 motif and Papain like protease virus proteins.Based on PyRx results, Mefloquine and Atovaquone have higher docking affinity scores against virus proteins compared to other antimalarial compounds. Screening report of Atovaquone exhibited affirmative inhibition constant on Spike protein SARS HR1 motif, 3CL and Papain like protease. In silico analysis reported Atovaquone as a promising candidate for COVID 19 therapy.

'Mucormycosis' A Fungal Infection Threatening India During COVID-19' - A Review

: During the second wave of Covid-19 in India, doctors recently reported a outbreak of cases involving a rare infection - called the "black fungus" - among recovering and recovered Covid-19 patients. The frequency of bacterial and fungal coinfections has been continuously rising. At the same time, invasive pulmonary aspergillosis is increasingly being recognized in association with nCOVID-19. Currently, India is suffering from a newly maiming disease associated with nCOVID-19 infected patients; at the time of the treatment, it can be developed into rhino-orbital mucormycosis. There are some approved antifungal therapies for treating this fungal infection. The background, risk factors, and associated reports about the infection are described in this review.

Pleuromutilin and its Derivatives: Promising Novel Anti-Infective Agents

: Due to the emergence and spread of the drug resistance to numerous antibiotics, global research attempts focus on new classes of antibiotics with different mechanisms of action from currently used drugs. Pleuromutilin was first identified as a natural antibiotic in 1951 from the New York Botanical Garden and Columbia University. The substance was isolated from Pleurotus mutilus and Pleurotus passeckerianus. Nevertheless, pleuromutilin was first launched in 1979 (tiamulin) for use in veterinarians. However, antibiotics with new targets or employ a different action mechanism are always attractive because they conquered recognized resistance by the bacteria and were not resisted against approved antibiotic classes. Pleuromutilin has a unique antibacterial activity that binds to the peptidyl transferase at the central area of the bacteria's 50S ribosome to inhibit protein synthesis. Pleuromutilin antibiotics have antimicrobial activity against Gram-positive pathogens. Besides, they cover some fastidious Gram-negative bacteria. As Gram-positive bacteria increased resistance against currently approved antibiotics, the pleuromutilin antibiotic was investigated to develop a systemically antibacterial drug to be used in humans. In 2006, lefamulin was developed and started to encounter studying for systemic infection in humans. Lefamulin is a semi-synthetic pleuromutilin antibiotic, and the US FDA approved it for community-acquired bacterial pneumonia (CABP) treatment in August 2019. This review will focus on this antibiotic's critical issues, the relevant bacterial spectrum activity, preclinical and clinical information, and potentially therapeutic properties of pleuromutilin antibiotic.

Combrestatin derivatives as microtubular assembly inhibitors at colchicine binding site

: Colchicine binding site in microtubules is among the most flourishing target for anticancer remedy. Microtubule inhibitor drugs, including combrestatin phosphate, paclitaxel and Vinca alkaloids, were formerly considered to exert their activity primarily by increasing or decreasing the cellular microtubule mass. This review describes the microtubular assembly along with the combrestatin derivatives as microtubules inhibitors, the structures of compounds known to interact with colchicines binding site, and their possible mechanism of action. Additionally, we have also discussed the utility of other heterocyclic rings and their combrestatin derivatives in treating cancer. Colchicines binding site represents a stimulating new molecular target in the design of combrestatin drugs.

Natural products in targeting Acanthamoeba spp

: Pathogenic Acanthamoeba is responsible for causing serious eye and fatal brain infections. A successful prognosis remains elusive despite advances in chemotherapeutics and supportive care. Natural products of medicinal value remain a promising source for drug development due to their broad-spectrum antimicrobial activities. Herein, we discuss anti-Acanthamoebic properties of natural products originating from plants, marine, and microbial sources that could be exploited as potential avenue for drug discovery against infections caused by Acanthamoeba.

Anti-HIV Integrase Inhibitors as New Candidates for the Treatment of COVID-19: A Narrative Literature Review

Background: The initial reports of a contagious novel Severe Acute Respiratory Syndrome – Coronavirus-2 (SARS-CoV-2) were proclaimed by Wuhan, Hubei province, China. This pathogen quickly became a health concern due to the World Health Organization's (WHO) alarm of its pandemic essence. Hence, there is an urgent need for efficacious and curative therapy against COVID-19. Objective: Theoretically, repurposing anti-viral drugs, specifically HIV treatments, could help the urgent need for treating COVID-19 due to the structural similarities of their critical enzyme substrates. Integrase inhibitors are a category of anti-HIV drugs that inhibit integrase strand transfer. In this review, we investigate the binding affinity and stability of raltegravir, dolutegravir, bictegravir, and elvitegravir in interactions with crucial enzymes of coronavirus. Methods: A literature search was conducted using scientific databases such as Web of Science, Medline (PubMed), Scopus, Google Scholar, and Embase from commencement to September 2020. The most relevant articles regarding the potential effects of integrase inhibitors against COVID-19 were gathered. Ultimately, ten original articles related to the searched terms were selected for this narrative review. Results: Apparently, in addition to the recent drugs prescribed to cure SARS-CoV-2, integrase inhibitors are promising drugs for repurposing in COVID-19 treatment. Several studies on raltegravir, dolutegravir, bictegravir and elvitegravir were conducted using virtual screening to guess either they are effective or not. Encouraging results were mostly reported for raltegravir and dolutegravir. Nevertheless, bictegravir and elvitegravir need more investigations. Conclusion: Further experimental and clinical studies of antiviral drugs are necessary to introduce appropriate treatment options for COVID-19.