Antimicrobial peptides: A plausible approach for COVID-19 treatment.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected >400 million people globally leading to >5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs). AREAS COVERED: This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed. EXPERT OPINION: Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.

Triumvirate to treat mucormycosis: Interplay of pH, metal ions and antifungal drugs

Mucormycosis is a rare fungal infection mainly affecting immunocompromised patients. Recently, an alarming rise in cases of mucormycosis was observed in patients undergoing COVID-19 treatment. Commonly, this fungal infection is caused by Rhizopus spp., Mucor spp., and Lichtheimia spp., although the genera of other Mucorales such as Saksenaea, Rhizomucor, Cunninghamella, and Apophysomyces may also be involved. A number of factors such as high concentration of zinc, iron and hypoxia induced acidosis promote the growth of fungi, thereby increasing the risk of mucormycosis multiple folds. Iron chelators (deferasirox and deferiprone) and zinc chelators (clioquinol, phenanthroline and N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethane-1,2-diamine) have been reported to inhibit the growth of fungi in a number of in vitro and animal studies. Correction of metabolic acidosis by administration of bicarbonate or glycine reduces the susceptibility of patients to the invasion by fungal species. However, these factors have largely been ignored while deciding the treatment strategy for mucormycosis and first line treatment for the management of mucormycosis continues to be the expensive lipid based formulation of amphotericin B. Treatment with isavuconazole which is proposed as the second choice is reported to be more cost effective. Therefore, it is proposed that a combination of antifungal agent (isavuconazole) with zinc and iron chelators (deferasirox and clioquinol respectively) along with alkalizer (glycine buffer) could be an effective and multi-target approach for the treatment of mucormycosis while being cost effective also.

OUTBREAK of novel corona virus disease (COVID-19): Antecedence and aftermath.

Outbreak of Coronavirus disease 2019 (COVID-19) started in mid of December 2019 and spread very rapidly across the globe within a month of its outbreak. Researchers all across the globe started working to find out its possible treatments. However, most of initiatives taken were based on various hypotheses and till date no successful treatments have been achieved. Some strategies adopted by China where existing antiviral therapy was initially used to treat COVID-19 have not given very successful results. Researchers from Thailand explored the use of combination of anti-influenza drugs such as Oseltamivir, Lopinavir and Ritonavir to treat it. In some cases, combination therapy of antiviral drugs with chloroquine showed better action against COVID-19. Some of the clinical studies showed very good effect of chloroquine and hydroxychloroquine against COVID-19, however, they were not recommended due to serious clinical toxicity. In some cases, use of rho kinase inhibitor, fasudil was found very effective. In some of the countries, antibody-based therapies have proved fairly successful. The use of BCG vaccines came in light; however, they were not found successful due to lack of full-proof mechanistic studies. In Israel as well as in other developed countries, pluristems allogeneic placental expanded cell therapy has been found successful. Some phytochemicals and nutraceuticals have also been explored to treat it. In a recent report, the use of dexamethasone was found very effective in patients suffering from COVID-19. Its effect was most striking among patients on ventilator. The research for vaccines that can prevent the disease is still going on. In light of the dynamic trends, present review focuses on etiopathogenesis, factors associated with spreading of the virus, and possible strategies to treat this deadly infection. In addition, it attempts to compile the recent updates on development of drugs and vaccines for the dreaded disease.