Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements.

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.

Mechanistic insight into anti-COVID-19 drugs: recent trends and advancements.

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has been established now to be a deadly disease afflicting the whole world with worst consequences on healthcare, economy and day-to-day life activities. Being a communicable disease, which is highly pathogenic in humans, causing cough, throat infection, breathing problems, high fever, muscle pain, and may lead to death in some cases especially those having other comorbid conditions such as heart or kidney problems, and diabetes. Finding an appropriate drug and vaccine candidate against coronavirus disease (COVID-19) remains an ultimate and immediate goal for the global scientific community. Based on previous studies in the literature on SARS-CoV infection, there are a number of drugs that may inhibit the replication of SARS-CoV-2 and its infection. Such drugs comprise of inhibitors of Angiotensin-Converting Enzyme 2 (ACE2), transmembrane Serine Protease 2 (TMPRSS2), nonstructural protein 3C-like protease, nonstructural RNA-dependent RNA polymerase (RdRp) and many more. The antiviral drugs such as chloroquine and hydroxychloroquine, lopinavir and ritonavir as inhibitors for HIV protease, nucleotide analogue remdesivir, and broad-spectrum antiviral drugs are available to treat the SARS-CoV-2-infected patients. Therefore, this review article is planned to gain insight into the mechanism for blocking the entry of SARS-CoV-2, its validation, other inhibition mechanisms, and development of therapeutic drugs and vaccines against SARS-CoV-2.

Efficacy and Safety of New and Emerging Drugs for COVID-19: Favipiravir and Dexamethasone.

PURPOSE OF REVIEW: The widespread respiratory disease of virus known as severe acute respiratory syndrome-coronavirus 2019 (SAR-CoV-2) had infected more than 200 countries and caused pandemic and havoc in the world. RECENT FINDINGS: The genome of the virus was sequenced rapidly to study its mechanism, epidemiology, drugs, and vaccines. Many drugs and vaccines are being studied by researchers to treat and prevent the SARS-CoV-2. Favipiravir and dexamethasone are repurposed drugs which showed therapeutic potential and pharmaceutical efficacy against SARS-CoV-2. SUMMARY: The review describes the path of favipiravir and dexamethasone from chemistry to mechanisms of action to combat SARS-CoV-2. In addition, the potential side effects are also summarized to study their potential to control corona virus 2019.

Ayurveda and Allopathic Therapeutic Strategies in Coronavirus Pandemic Treatment 2020.

Purpose of Review: In the last month of 2019, i.e., December, COVID-19 hit Wuhan city in China. Since then, it has infected more than 210 countries and nearly about 33.4 million people with one million deaths globally. It is a viral disease with flu-like symptoms; hence, prevention and management is the best option to be adopted for its cure. Recent Findings: Many healthcare systems, scientists, and researchers are fighting for the cure of this pandemic. Ayurvedic and allopathic treatments have been studied extensively and approached for the cure of COVID-19. In addition to ayurvedic treatments, the Ministry of Ayush, India, has also recommended many remedies to boost up immunity. Allopathic studies involved several antiviral drugs which were used in different combinations for the treatment of COVID-19. Summary: Comparative analysis of Ayurveda and allopathic treatment strategies were carried out in the present study. Depending upon the patient's conditions and symptoms, Ayurveda is useful for the treatment of COVID-19. Allopathic treatments inhibit viral infection by targeting majorly endocytosis, and angiotensin-converting enzyme (Ace) receptor signaling. In this article, we summarize different ayurvedic and allopathic medicines and treatment strategies which have been used for the treatment of COVID-19, a global pandemic.

COVID-19 Pandemic: from Molecular Biology, Pathogenesis, Detection, and Treatment to Global Societal Impact.

PURPOSE OF REVIEW: In December 2019, there was an outbreak of viral disease in Wuhan, China which raised the concern across the whole world. The viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or novel coronavirus or COVID-19 (CoV-19) is known as a pandemic. After SARS-CoV and Middle East respiratory syndrome (MERS)-related CoV, COVID-19 is the third most pathogenic virus, hazardous to humans which have raised worries concerning the capacity of current security measures and the human services framework to deal with such danger. RECENT FINDINGS: According to WHO, the mortality rate of COVID-19 exceeded that of SARS and MERS in view of which COVID-19 was declared as public health emergency of international concern. Coronaviruses are positive-sense RNA viruses with single stranded RNA and non-segmented envelopes. Recently, genome sequencing confirmed that COVID-19 is similar to SARS-CoV and bat coronavirus, but the major source of this pandemic outbreak, its transmission, and mechanisms related to its pathogenicity to humans are not yet known. SUMMARY: In order to prevent the further pandemic and loss to humanity, scientists are studying the development of therapeutic drugs, vaccines, and strategies to cure the infections. In this review, we present a brief introduction to emerging and re-emerging pathogens, i.e., coronavirus in humans and animals, its taxonomic classification, genome organization, its replication, pathogenicity, impact on socioeconomic growth, and drugs associated with COVID-19.

Mycobacterium aurum is Unable to Survive Mycobacterium tuberculosis Latency Associated Stress Conditions: Implications as Non-suitable Model Organism.

Mycobacterium tuberculosis manages to remain latent in the human body regardless of extensive chemotherapy. Complete eradication of tuberculosis (TB) requires treatment strategies targeted against latent form of infection, in addition to the current regimen of antimycobacterials. Many in vitro and in vivo models have been proposed to imitate latent TB infection, yet none of them is able to completely mimic latent infection state of M. tuberculosis. Highly infectious nature of the pathogen requiring BSL3 facilities and its long generation time further add to complications. M. aurum has been proposed as an important model organism for high throughput screening of drugs and exhibits high genomic similarity with that of M. tuberculosis. Thus, the present study was undertaken to explore if M. aurum could be used as a surrogate organism for studies related to M. tuberculosis latent infection. M. aurum was subjected to in vitro conditions of oxygen depletion, lack of nutrients and acidic stress encountered by latent M. tuberculosis bacteria. CFU count of M. aurum cells along with any change in cell shape and size was recorded at regular intervals during the stress conditions. M. aurum cells were unable to survive for extended periods under all three conditions used in the study. Thus, our studies suggest that M. aurum is not a suitable organism to mimic M. tuberculosis persistent infection under in vitro conditions, and further studies are required on different species for the establishment of a fast growing species as a suitable model for M. tuberculosis persistent infection.

A lacZ Reporter-Based Strategy for Rapid Expression Analysis and Target Validation of Mycobacterium tuberculosis Latent Infection Genes.

We report a novel lacZ fusion vector and demonstrate its utility for expression analysis of genes associated with Mycobacterium tuberculosis latent infection. The vector contains E. coli (oriE) and mycobacterial (oriM) origins of replication, a kanamycin resistance gene (Km(r)) as selection marker, and a lacZ reporter gene in fusion with MCS for cloning of upstream regulatory sequence of the desired genes. ß-galactosidase activity of the vector was standardized for expression analysis under latent mycobacterial conditions using Phsp60, a constitutive mycobacterial promoter, utilizing Mycobacterium smegmatis as model organism. Validation of the vector was done by cloning and expression analysis of PhspX (alpha crystalline) and Picl (isocitrate lyase), promoters from two of the genes shown to be involved in M. tuberculosis persistence. Both genes showed appreciable levels of ß-galactosidase expression under hypoxia-induced persistent conditions in comparison to their actively replicating state. Expression analysis of a set of hypothetical genes was also done, of which Rv0628c showed increased expression under persistent conditions. The reported fusion vector and the strategy can be effectively used for short listing and validation of drug targets deduced from various non-conclusive approaches such as bioinformatics and microarray analysis against latent/persistent form of mycobacterial infection.

Cytomorphology of lung metastasis of pure choriocarcinoma of testis in a 58-year-old male.

Choriocarcinoma is malignancy arising from the trophoblastic tissue. Pure choriocarcinoma is rare in testis. Choriocarcinoma of testis is more commonly associated with other germ cell tumors. The usual age of presentation is 2nd-3rd decade. Distant metastasis is known to occur in choriocarcinoma. We present a rare case of testicular pure choriocarcinoma in a male patient. The patient was treated with orchidectomy, lymphadenectomy, and chemotherapy. Three months later the patient presented with hemoptysis and a lung mass. The aspiration cytology of the lung mass revealed metastatic deposits of syncytiotrophoblastic and cytiotrophoblastic cells. We are reporting this case due to its rarity, rare age of presentation, and characteristic cytology at metastatic focus.

Antibiogram and characterization of resistance markers among Escherichia coli Isolates from urinary tract infections.

INTRODUCTION: Urinary tract infection is the most frequently diagnosed kidney and urologic disease, and Escherichia coli is by far its most common etiological agent. Uropathogenic E. coli are responsible for approximately 90% of urinary tract infections seen in individuals with ordinary anatomy therefore, it is essential to review the antibiogram of uropathogenic E. coli periodically to help clinicians decide on the appropriate therapy. METHODOLOGY: We evaluated E. coli isolated from urinary tract infections at the National Salmonella and Escherichia Centre for antibiogram, plasmid transferability and stability of resistance markers. RESULTS: In total, 90.9% of the isolates were found to be sensitive to nitrofurantoin while the highest proportion of the isolates was found to be resistant to nalidixic acid. Minimum inhibitory concentrations of all antimicrobials for different isolates were well within the limits specified by the Clinical and Laboratory Standards Institute.  Resistance against tetracycline was not transferred either by conjugation and transformation. Streptomycin resistance was found to be lost in the maximum number of tested isolates showing loss at the 10th, 15th and 20th passages. CONCLUSION: Changing trends in antibiotic resistance necessitates the periodic generation of antibiogram data to help health authorities revise treatment strategies for urinary tract infections caused by E. coli.

Small bowel adenocarcinoma in Crohn's disease.

Small bowel neoplastic disease is a rare but dreaded occurrence in Crohn's disease (CD) and the diagnosis is often disguised by nonspecific and varied presenting symptoms mimicking active or obstructive CD. As such, the diagnosis is all too often delayed, typically detected at a late stage, and with a poor prognosis. CD has become a well-recognized risk factor for the development of small bowel adenocarcinoma. The data, however, are limited and based on case reports, retrospective studies, and review of the literature.

Helicobacter pylori.

PURPOSE OF REVIEW: Helicobacter pylori is an important human pathogen, responsible for most peptic ulcer disease, gastritis and gastric malignancies. H. pylori has several unique features: it is highly adapted for gastric colonization, yet it produces clinical consequences in a small minority, its genome is known, and it is the only bacterium strongly associated with cancer. H. pylori is therefore of great interest to clinicians and researchers of many, often disparate, disciplines. We highlight recent advances in this fast changing field from many different areas. RECENT FINDINGS: The major contentious clinical issues relate to the synergistic gastrotoxic interactions of H. pylori with non-steroidal anti-inflammatory drugs, and a possible association of H. pylori with atherosclerotic events. Accumulating evidence implicates genetic variation in the inflammatory response to H. pylori in the etiology of the increased risk of gastric cancer after H. pylori infection. Studies of pathogenesis have been aided by increasingly sophisticated murine models. The effects in gastric epithelial cells of two of the major virulence factors (genes within the cag pathogenicity island and the vacuolating cytotoxin, VacA) of H. pylori illustrate the complex network of cellular reactions activated by H. pylori. The metabolism of H. pylori is dependent on the availability of hydrogen. SUMMARY: Basic science research into H. pylori continues to elucidate the mechanisms by which H. pylori infection causes disease. These findings have implications for the design of novel therapies and for improving clinical strategies to identify at-risk individuals. Many are also worthy of consideration for other epithelial-microbial interactions.