A Comprehensive Review on Monkeypox Viral Disease with Potential Diagnostics and Therapeutic Options.

The purpose of this review is to give an up-to-date, thorough, and timely overview of monkeypox (Mpox), a severe infectious viral disease. Furthermore, this review provides an up-to-date treatment option for Mpox. The monkeypox virus (MPXV) has remained the most virulent poxvirus for humans since the elimination of smallpox approximately 41 years ago, with distribution mainly in central and west Africa. Mpox in humans is a zoonotically transferred disease that results in symptoms like those of smallpox. It had spread throughout west and central Africa when it was first diagnosed in the Republic of Congo in 1970. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease's global significance. A better understanding of Mpox's dynamic epidemiology may be attained by increased surveillance and identification of cases.

An Updated Review on Monkeypox Viral Disease: Emphasis on Genomic Diversity.

Monkeypox virus has remained the most virulent poxvirus since the elimination of smallpox approximately 41 years ago, with distribution mostly in Central and West Africa. Monkeypox (Mpox) in humans is a zoonotically transferred disease that results in a smallpox-like disease. It was first diagnosed in 1970 in the Democratic Republic of the Congo (DRC), and the disease has spread over West and Central Africa. The purpose of this review was to give an up-to-date, thorough, and timely overview on the genomic diversity and evolution of a re-emerging infectious disease. The genetic profile of Mpox may also be helpful in targeting new therapeutic options based on genes, mutations, and phylogeny. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease's global significance. Increased monitoring and identification of Mpox cases are critical tools for obtaining a better knowledge of the ever-changing epidemiology of this disease.

Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review.

Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.

Psychogenetic, genetic and epigenetic mechanisms in Candida auris: Role in drug resistance.

In recent years, we are facing the challenge of drug resistance emergence in fungi. The availability of limited antifungals and development of multi-drug resistance in fungal pathogens has become a serious concern in the past years in the health sector. Although several cellular, molecular, and genetic mechanisms have been proposed to explain the drug resistance mechanism in fungi, but a complete understanding of the molecular and genetic mechanisms is still lacking. Besides the genetic mechanism, epigenetic mechanisms are pivotal in the fungal lifecycle and disease biology. However, very little is understood about the role of epigenetic mechanisms in the emergence of multi-drug resistance in fungi, especially in Candida auris (C. auris). The current narrative review summaries the clinical characteristics, genomic organization, and molecular/genetic/epigenetic mechanisms underlying the emergence of drug resistance in C. auris. A very few studies have attempted to evaluate the role of epigenetic mechanisms in C. auris. Furthermore, advanced genetic tools such as the CRISP-Cas9 system can be utilized to elucidate the epigenetic mechanisms and their role in the emergence of multi-drug resistance in C. auris.

Genetic Variants and Protective Immunity against SARS-CoV-2.

The novel coronavirus-19 (SARS-CoV-2), has infected numerous individuals worldwide, resulting in millions of fatalities. The pandemic spread with high mortality rates in multiple waves, leaving others with moderate to severe symptoms. Co-morbidity variables, including hypertension, diabetes, and immunosuppression, have exacerbated the severity of COVID-19. In addition, numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an individual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection. This review investigated the host genetic components implicated at the various stages of viral pathogenesis, including viral entry, pathophysiological alterations, and immunological responses. In addition, the recent and most updated genetic variations associated with multiple host factors affecting COVID-19 pathogenesis are described in the study.

Recent Trends and Developments in Multifunctional Nanoparticles for Cancer Theranostics.

Conventional anticancer treatments, such as radiotherapy and chemotherapy, have significantly improved cancer therapy. Nevertheless, the existing traditional anticancer treatments have been reported to cause serious side effects and resistance to cancer and even to severely affect the quality of life of cancer survivors, which indicates the utmost urgency to develop effective and safe anticancer treatments. As the primary focus of cancer nanotheranostics, nanomaterials with unique surface chemistry and shape have been investigated for integrating cancer diagnostics with treatment techniques, including guiding a prompt diagnosis, precise imaging, treatment with an effective dose, and real-time supervision of therapeutic efficacy. Several theranostic nanosystems have been explored for cancer diagnosis and treatment in the past decade. However, metal-based nanotheranostics continue to be the most common types of nonentities. Consequently, the present review covers the physical characteristics of effective metallic, functionalized, and hybrid nanotheranostic systems. The scope of coverage also includes the clinical advantages and limitations of cancer nanotheranostics. In light of these viewpoints, future research directions exploring the robustness and clinical viability of cancer nanotheranostics through various strategies to enhance the biocompatibility of theranostic nanoparticles are summarised.

Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.

Promising Antimycobacterial Activities of Flavonoids against Mycobacterium sp. Drug Targets: A Comprehensive Review.

Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers' interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review.

The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available to combat SARS-CoV-2. However, there has been an increase in virus-related research, including exploring new drugs and their repurposing. Since discovering penicillin, natural products, particularly those derived from microbes, have been viewed as an abundant source of lead compounds for drug discovery. These compounds treat bacterial, fungal, parasitic, and viral infections. This review incorporates evidence from the available research publications on isolated and identified natural products derived from microbes with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties. About 131 compounds with in vitro antiviral activity and 1 compound with both in vitro and in vivo activity have been isolated from microorganisms, and the mechanism of action for some of these compounds has been described. Recent reports have shown that natural products produced by the microbes, such as aurasperone A, neochinulin A and B, and aspulvinone D, M, and R, have potent in vitro anti-SARS-CoV-2 activity, targeting the main protease (Mpro). In the near and distant future, these molecules could be used to develop antiviral drugs for treating infections and preventing the spread of disease.

The genetic environment of the antiseptic resistance genes qacEΔ1 and cepA in Klebsiella pneumoniae.

The genetic environment of two antiseptic resistance genes (qacEΔ1 and cepA) was examined in Klebsiella pneumoniae isolates obtained from the Royal Infirmary of Edinburgh between 2006 and 2008. In 4 of 34 isolates, which carried the qacEΔ1 gene, the sul1 gene was located immediately downstream. In two of these, the orf5 gene of unknown function was found immediately downstream of the sul1 gene. In one case, this was substituted by the chrA gene. The cepA gene was carried by 56 (87·5%) isolates, and the pfkA gene was found directly downstream in 45 (70·3%) isolates, and in 40 (62·5%) of these isolates, the menG gene was found directly downstream. The cpxP gene was found in 47 (73·4%) isolates upstream of the cepA, and in 35 of these isolates, the cpxR gene was identified. These latter genes are transcription regulators, and reverse transcription polymerase chain reaction (RT-PCR) revealed that their presence was associated with cepA expression.