Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

Background: Community-acquired bacterial pneumonia (CABP) remains a global public health threat and is a leading cause of hospitalization and infection-linked mortality. Levonadifloxacin is a novel benzoquinolizine antibiotic with a broad-spectrum activity including methicillin-resistant Staphylococcus aureus (MRSA) and CABP-pathogens. Methods: This multi-centre, retrospective, post-marketing, real-world study assessed the efficacy and safety of levonadifloxacin oral and/or intravenous therapy in the treatment of CABP. Data from 338 patients above 17 years-of-age who received levonadifloxacin (oral or intravenous or both) was collected from 89 healthcare facilities across India. Information on clinical condition, comorbidities, complications, and details of concurrent therapy (including antimicrobial agents) was also collected. Study outcomes were clinical and microbial success at the end of therapy while safety was assessed based on clinical and laboratory adverse events. Results: Of the 338 patients, 244 (72.2%) were male, 93 (27.5%) were female and 1 (0.43%) was a transgender. About 294 (87.0%) patients were hospital-treated and 44 (13%) received outpatient treatment. About 248 (73.4%) patients received intravenous levonadifloxacin treatment, 79 (23.4%) received oral and 11 (3.3%) received intravenous followed by oral levonadifloxacin therapy. The common comorbid conditions were diabetes (14.2%) and hypertension (8.6%). Mean duration of levonadifloxacin therapy was 6.4 days. Clinical and microbial success in levonadifloxacin-treated patients was 95.0% (321/388) and 96.8% (150/155), respectively. Conclusions: Levonadifloxacin showed promising clinical outcomes and safety when used as an intravenous and/or oral for the treatment of CABP, both in outpatients as well as hospitalized patients.

The antibacterial activity of isatin hybrids

: Bacterial infections which cause a wide range of host immune disorders leading to local and systemic tissue damage, are still one of the main causes of patient morbidity and mortality worldwide. Treatment of bacterial infections is challenging, which is mainly attributed to the rapidly evolving resistance mechanisms, creating an urgent demand to develop novel antibacterial agents. Hybridization is one of the most promising strategies in the development of novel antibacterial drugs with the potential to address drug resistance since different pharmacophores in the hybrid molecules could modulate multiple targets and exert synergistic effects. Isatin, distributed widely in nature, can exert antibacterial properties through acting on diverse enzymes, proteins, and receptors. Accordingly, hybridization of isatin pharmacophores with other antibacterial pharmacophores in one molecule may provide novel antibacterial candidates with broad-spectrum activity against various pathogens, including drug-resistant forms. This review aims to outline the recent advances of natural and synthetic isatin hybrids with antibacterial potential and summarize the structure-activity relationship (SAR) to provide an insight for the rational design of more active candidates, covering articles published between January 2012 and June 2021.

Neutralizing antibodies for the prevention and treatment of COVID-19

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus–cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

Review on Abhrasindoora: A Sublimated Mercurial Formulation as a Herbo-Bio-Mineral Metallic Compound for Respiratory Ailments

Abhrasindoora is a unique mercurial formulation as a herbo-bio-mineral metallic compound which is mentioned under Kupipakwa Rasayana Prakarana in Rasendra Sambhava. There are four formulations are mentioned with the name of Abhrasindoora, amongst them one in Rasendra Shambhava and three in Rasayogasagara. In this review article we have focused on the specific method mentioned in Rasendra Sambhava, which is a combination of Dhanyabhraka, Shodhita Parada (Mercury), Shodhita Gandhaka (Sulphur) in equal proportion (1:1:1). Its method of preparation initiates with the Kajjali formation followed by impregnation of Latex of Calotropis procera (QS) and freshly expressed arial root juice of Ficus bengalensis (QS) and cooking into mud smeared seven layered glass bottle using sand bath heating system. Specific heating pattern consisting of mild (1200C-2500C) moderate (2500C-4500C) and intense (4500C-6500C) heat should be maintained for preparation of Abhrasindoora. Previous pharmaceutical study done by Dr. Jyoti B. (2018) had yielded approximately 28% bright red color Abhrasindoora. In Rasayogasagara, bhasmikarana process is mentioned for preparation of Abhrasindoora which is not appropriate as per current trend. Hence, Rasendra Sambhava method is appropriate to prepare Abhrasindoora. This formulation has broad spectrum activity along with suitable adjuvants. The therapeutic indications are Cough, Bronchial Asthma, Fever etc. This herbo-bio-mineral metallic compound is quick acting, low dose, highly stable, good palatability and helps to treats chronic ailments.

Exploration of Culturable Marine Streptomyces from Southern Coastal Region of India with Antibacterial Properties

The Southern coastal region is a geographically positioned area with rich source of microbial diversity, of which producing broad spectrum of bioactive compounds. The marine sediments are collected from the various sites of south east coastal region of Tamil nadu and are processed. Out of 78 isolates, the 4 strains of actinomycetes are showing broad spectrum activity against Klebsiella pneumoniae (MTCC 1687), Proteus vulgaris (MTCC 3160), Salmonella typhi (MTCC 3231), Shigella dysenteriae (MTCC 3642) and Vibrio cholerae (MTCC 3906). The bioactive isolates are proceeded for further morphological features like growth pattern and mycelial coloration, biochemical and polyphasic taxonomical characterisation were documented. Isolates are investigated for abiotic stress condition to study the growth rate of isolates. Finally, the 16S rRNA molecular identification and phylogenetic analysis of the isolates were explored. Further, bioactive isolates may be potential source for discovery of molecules with industrial applications.

Antiviral Activity of Umifenovir In Vitro against a Broad Spectrum of Coronaviruses, Including the Novel SARS-CoV-2 Virus

An escalating pandemic of the novel SARS-CoV-2 virus is impacting global health, and effective antivirals are needed. Umifenovir (Arbidol) is an indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It has been shown that umifenovir has broad spectrum activity against different viruses. We evaluated the sensitivity of different coronaviruses, including the novel SARS-CoV-2 virus, to umifenovir using in vitro assays. Using a plaque assay, we revealed an antiviral effect of umifenovir against seasonal HCoV-229E and HCoV-OC43 coronaviruses in Vero E6 cells, with estimated 50% effective concentrations (EC50) of 10.0 ± 0.5 µM and 9.0 ± 0.4 µM, respectively. Umifenovir at 90 µM significantly suppressed plaque formation in CMK-AH-1 cells infected with SARS-CoV. Umifenovir also inhibited the replication of SARS-CoV-2 virus, with EC50 values ranging from 15.37 ± 3.6 to 28.0 ± 1.0 µM. In addition, 21–36 µM of umifenovir significantly suppressed SARS-CoV-2 virus titers (≥2 log TCID50/mL) in the first 24 h after infection. Repurposing of antiviral drugs is very helpful in fighting COVID-19. A safe, pan-antiviral drug such as umifenovir could be extremely beneficial in combating the early stages of a viral pandemic.

Small-molecule ligands can inhibit −1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses

Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases since 2000 have high-lighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored a group of 6 small-molecule ligands, evaluating their activity against the frameshift signals from a panel of representative bat CoVs—the most likely source of future zoonoses—as well as SARS-CoV-2 and MERS-CoV. We found that whereas some ligands had notable activity against only a few of the frameshift signals, the serine protease inhibitor nafamostat suppressed −1 PRF significantly in several of them, while having limited to no effect on −1 PRF caused by frameshift signals from other viruses used as negative controls. These results suggest it is possible to find small-molecule ligands that inhibit −1 PRF specifically in a broad spectrum of CoVs, establishing the frameshift signal as a viable target for developing pan-coronaviral therapeutics.

Efficacy of some medicated soaps and hand washes available in market

Background: Handwashing is underlined as the absolute most significant measure to forestall cross-transmission of small-scale life forms and consequently to forestall nosocomial contaminations. Be that as it may, under routine emergency clinic practice consistent with this measure is still unsatisfactorily low, under half in many investigations distributed in the previous 20 years. This consistent finding is stressing because ongoing investigations have demonstrated that this degree of consistency won't decrease the danger of transmission of multi- medicate safe microscopic organisms in the emergency clinics. Results: In the present investigation effect of marketed hand washed namely Lifebuoy, Dettol and Savlon were tested on bacteria E. coli, S.aureus, S.pyogen, Klebshiella and, fungi Candida albicans. All the handwash at concentrated level found to be effective but only Dettol hand wash could give inhibitory action at 25ug/ml against Klebshiella while others at50ug/ml. Conclusions: Soapex and Dettol soap had broad spectrum activity as it inhibited the growth of Gram positive (Streptococcus pyogen) and Gram-negative (Escherichia coli). Liquid handwash such as Lifebuoy,Dettol and Savlon showed broad spectrum activity on both Gram-positive and Gram negative test microorganisms.