Anti-Infective Agents - Volume 20, Issue 2, 2022

Background: Coronaviruses including COVID-19, MERS and SARS have affected millions of people around the world since their emergence. Still, there is not a certain drug treatment strategy for coronaviruses. Objective: This review aims at a compilation of a comprehensive study on literature reporting the treatment strategies and regimens used for COVID-19, MERS and SARS with an emphasis on the clinical trials and experimentations. Results: According to the literature, the most effective drugs reported so far for treatment strategies include: lopinavir/ritonavir, favipiravir, ribavirin, oseltamivir, remdesivir, hydroxychloroquine, herbal extracts, monoclonal antibodies and anticytokine agents. Some combinations of drugs have been very effective to reduce the death rate, hospitalization stay and to prevent the progress of the disease to the later critical and severe stages. Conclusions: However, a combination of drugs and regimens have been useful and saved millions of patient’s lives but the clinical data reviewed in this essay indicate that the current drugs do not make an impervious barrier against coronavirus infections and cannot protect or treat patients completely. Therefore, there is a much demand for the discovery and introduction of new antiviral drugs.

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 employing 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 semisynthetic 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.

Coronavirus disease-2019 (COVID-19) has gained much popularity not only in the Wuhan city of China but internationally also; in January 2020, the corona rapidly spread to many countries like the USA, Italy, Russia, India, Singapore, Pakistan, Thailand, Canada, Australia, England, and so on through passengers traveling to other countries. Corona patients can be cured with synthetic drugs, traditional herbal medicines (THM), use of Vitamin D and the quarantine approach. Different allopathic medicines, herbal extracts, and vitamin D have been observed to be useful in the treatment of novel coronavirus, like Remdesivir, hydroxychloroquine, Teicoplanin, Lopinavir+ Ritonavir, Ribavirin + corticosteroids, Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. Various antiviral drugs are used to treat COVID-19, alone or in combination with other medications like Interferon-α, Lopinavir + Ritonavir, Arbidol, corticosteroids, etc., and some herbal extracts; also quarantine approach and Vitamin D are used that not only cure the infection but also boost up our immunity. For this review article, different papers were searched on Google Scholar, Scopus, WHO’s website, PubMed, clinicaltrials.gov and other relevant scientific research websites. In this review article, we have discussed the current strategies that are being used to treat COVID-19. Along with allopathic drugs, some herbal extracts can also be used to treat this novel coronavirus, like Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. and even vitamin D.

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 meet 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.

Background: Coronavirus disease (COVID-19) is a severe acute respiratory condition that has affected millions of people worldwide, indicating a global health emergency. Despite the deteriorating trends of COVID-19, no drugs are validated to have substantial efficacy in the potential treatment of COVID-19 patients in large-scale trials. Methods: This study aimed at identifying potential antimalarial candidate molecules for the treatment of COVID and evaluating the possible mechanism of action by in silico screening method. In silico screening studies on various antimalarial compounds, like amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine, and atovaquone, were conducted using PyRx and AutoDoc 1.5.6 tools against ACE 2 receptor, 3CL protease, hemagglutinin esterase, spike protein of SARS HR1 motif, and papain-like protease virus proteins. Results: Based on PyRx results, mefloquine and atovaquone were found to have higher docking affinity scores against virus proteins compared to other antimalarial compounds. Screening report of atovaquone exhibited affirmative inhibition constant for spike protein of SARS HR1 motif, 3CL protease, and papain-like protease. Conclusion: In silico analysis reported atovaquone as a promising candidate for COVID 19 therapy.

Viral infections are a major threat to the aquaculture industry throughout the world. Betanodavirus is one of the most infectious viruses that cause the highest mortality in larval and juvenile stages of Latescalcarifer commonly known as Barramundi. It is a single-stranded positive- sense RNA virus and causes viral nervous necrosis(VNN).VNN is caused by a RNA virus that gets transmitted both horizontally and vertically so the most effective method against this virus is to vaccinate the fish, however, vaccination becomes difficult since the disease is associated with outbreaks in larval and juvenile stages which are not that much immunocompetent. In our previous in silico studies, we proved the stability of camphene as a better phytochemical agent. In continuation to prove the authenticity of camphene as a potential antiviral agent against betanodavirus, its in vitro validation was performed. Sea bass kidney cell line (SISK) was selected for carrying out the in vitro studies and cytotoxicity studies of camphene in the SISK were done by MTT assay. Based on the analysis of the MTT assay, different dosages of camphene were selected viz.,0.2, 0.5, 1, 1.5, 2, 2.5, 5, 10, 20, 30 μg/ml. The SISK cells were infected with a virus inoculum(200μl). Further, the antiviral activity of camphene on infected SISK cells by Betanodaviruswas elucidated with the help of quantitative Real-time PCR(qPCR) on the 3rd and 5th day of infection. Analysis of results depicted that the dose of camphene 2 to 10 μg/ml is the safest dose against Betanodavirus. Hence this is aptly revealed that camphene can be used as a potential antiviral agent against Betanodavirus.

Background: Despite the global increase of CTX-M type Extended-Spectrum-β-Lactamases (ESBLs) in recent years among Enterobacteriaceae isolates from urinary tract infections, little data is available from Nepal. Objective: This study was conducted to detect the genes encoding extended-spectrum β-lactamases among Enterobacteriaceae isolated from the urine samples from Nepal. Methods: A total of 148 Enterobacteriaceae isolates were obtained from urine samples in Annapurna Neurological Institute and Allied Sciences from July 2016 to June 2017. ESBL production was detected according to the Clinical and Laboratory Standards Institute (CLSI) recommended method. PCR and sequencing were used for the detection of ESBL genes. Results: Overall, 24.3% (36/148) of the study isolates were positive for ESBL production. E. coli was the predominant ESBL-producing organism (28.8%). ESBL-producing organisms showed a high rate of resistance to ceftazidime (58.4%), cefepime (91.7%), aztreonam (83.4%), and ciprofloxacin (80.6%). Also, 30.6% of ESBL-producing organisms were multi-drug resistant. All ESBL producers were CTX-M positive; other ESBL genes were not detected. The majority of the ESBL positive organisms produced CTX-M-15 (n= 31) and few organisms (n= 5) were CTX-M-27 producers. Conclusion: The present study shows that the predominant CTX-M type ESBL in our hospital setting is CTX-M-15.