Crisis averted: a world united against the menace of multiple drug-resistant superbugs -pioneering anti-AMR vaccines, RNA interference, nanomedicine, CRISPR-based antimicrobials, bacteriophage therapies, and clinical artificial intelligence strategies to safeguard global antimicrobial arsenal.

The efficacy of antibiotics and other antimicrobial agents in combating bacterial infections faces a grave peril in the form of antimicrobial resistance (AMR), an exceedingly pressing global health issue. The emergence and dissemination of drug-resistant bacteria can be attributed to the rampant overuse and misuse of antibiotics, leading to dire consequences such as organ failure and sepsis. Beyond the realm of individual health, the pervasive specter of AMR casts its ominous shadow upon the economy and society at large, resulting in protracted hospital stays, elevated medical expenditures, and diminished productivity, with particularly dire consequences for vulnerable populations.

Potential Immunogenic Activity of Computationally Designed mRNA- and Peptide-Based Prophylactic Vaccines against MERS, SARS-CoV, and SARS-CoV-2: A Reverse Vaccinology Approach.

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses.

Computational Evaluation of Abrogation of HBx-Bcl-xL Complex with High-Affinity Carbon Nanotubes (Fullerene) to Halt the Hepatitis B Virus Replication.

Hepatitis B virus (HBV) is the world's most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target.

Rational design of potent anti-COVID-19 main protease drugs: An extensive multi-spectrum in silico approach.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a novel coronavirus and the etiological agent of global pandemic coronavirus disease (COVID-19) requires quick development of potential therapeutic strategies. Computer aided drug design approaches are highly efficient in identifying promising drug candidates among an available pool of biological active antivirals with safe pharmacokinetics. The main protease (M) enzyme of SARS-CoV-2 is considered key in virus production and its crystal structures are available at excellent resolution.

Multiepitope Subunit Vaccine Design against COVID-19 Based on the Spike Protein of SARS-CoV-2: An Analysis.

The global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, has resulted in a negative impact on human health and on social and economic activities worldwide. Researchers around the globe need to design and develop successful therapeutics as well as vaccines against the novel COVID-19 disease. In the present study, we conducted comprehensive computer-assisted analysis on the spike glycoprotein of SARS-CoV-2 in order to design a safe and potent multiepitope vaccine.

A computational study to disclose potential drugs and vaccine ensemble for COVID-19 conundrum.

The nucleocapsid (N) protein of SARS-COV-2, a virus responsible for the current COVID-19 pandemic, is considered a potential candidate for the design of new drugs and vaccines. The protein is central to several critical events in virus production, with its highly druggable nature and rich antigenic determinants making it an excellent anti-viral biomolecule. Docking-based virtual screening using the Asinex anti-viral library identified binding of drug molecules at three specific positions: loop 1 region, loop 2 region and β-sheet core pockets, the loop 2 region being the most common binding and stable site for the bulk of the molecules.

Familial clustering of hepatitis C virus in a Pakistani population.

Pakistan has the second-highest burden of hepatitis C patients in the world. A total of 683 individuals, who visited the Liver Clinic during the study period, were screened for the presence of hepatitis C virus (HCV) infection. A total of 534 individuals who showed positive HCV infection were grouped into the case group and 149 individuals with HCV negative status were grouped into the control group.

Relationship of S/R warfarin ratio with CYP2C9 genotypes in Pakistani population.

Warfarin is administered as a racemic preparation of R- and S-enantiomers. S-warfarin is more potent than R-warfarin, so changes in blood levels of S-warfarin affect the anticoagulant response. This study was carried out to determine the effect of CYP2C9*2 and CYP2C9*3 polymorphisms on S/R warfarin ratio.

The World after Ebola: An Overview of Ebola Complications, Vaccine Development, Lessons Learned, Financial Losses, and Disease Preparedness.

The 2014-2016 Ebola outbreak in West Africa was the largest of its kind with 11,000 deaths and approximately 28,637 affected cases. The aim of the study was to analyze the global situation after the Ebola outbreak including Ebola complications, vaccine development, lessons learned, financial losses, and disease preparedness. We searched in PubMed, Google, and Google Scholar by using keywords Ebola virus, Ebola vaccine development and Ebola virus transmission, the world after Ebola, financial losses by Ebola outbreak, and disease preparedness.

Evaluation of Three Rapid Screening Tests for Detection of Hepatitis C Antibodies on Mass Scale.

Hepatitis C virus (HCV) is a leading health problem across the globe. Only 20% of HCV positive individuals know their positive disease status. Effective HCV screening tests are required to screen both general and high-risk populations and identify the silent cases of HCV.

Hepatitis elimination by 2030: Progress and challenges.

Globally, over 300 million people are living with viral hepatitis with approximately 1.3 million deaths per year. In 2016, World Health Assembly adopted the Global Health Sector Strategy on viral hepatitis to eliminate hepatitis by 2030.

Prediction of promiscuous T cell epitopes in RNA dependent RNA polymerase of Chikungunya virus.

Objective: To explore RNA dependent RNA polymerase of Chikungunya virus (CHIKV) and develop T cell based epitopes with high antigenicity and good binding affinity for the human leukocyte antigen (HLA) classes as targets for epitopes based CHIKV vaccine.

Methods: In this study we downloaded 371 non-structural protein 4 protein sequences of CHIKV belonging to different regions of the world from the US National Institute of Allergy and Infectious Diseases (NIAID) virus pathogen resource database. All the sequences were aligned by using CLUSTALW software and a consensus sequence was developed by using Uni Pro U Gene Software version 1.

Prevalence of hepatitis C in people who inject drugs in the cities of Rawalpindi and Islamabad, Pakistan.

Pakistan has the second highest burden of hepatitis C (HCV) in the world. The major route of HCV transmission is contaminated blood or needle sharing. Seventy percent of people who inject drugs (PWIDs) shared needles at some time in their addiction history.

Frequency of Common VKORC1 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population.

Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead to interindividual variability in warfarin dose requirement. The characterization of genotype frequency distribution is required in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common VKORC1 polymorphisms to warfarin therapy.

Frequency of Common CYP2C9 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population.

Polymorphisms in cytochrome P450 (CYP) 2C9 (CYP2C9) gene result in interindividual variability in warfarin dose requirement. There is a need for characterization of genotype frequency distribution in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common CYP2C9 polymorphisms to warfarin therapy.

EFFECT OF NEBIVOLOL ON TONE OF TRACHEAL MUSCLE OF GUINEA PIG.

Background: The use of β-blockers is limited by adverse effects such as bronchospasm in asthmatics. Third generation β-blockers such as nebivolol may show better tolerability in asthmatic subjects because they lack β-blocker induced bronchoconstriction. Methods: Effects of nebivolol on the tracheal muscle strips prepared from ovalbumin-sensitised guinea pigs of both sexes were studied.

Determination of S- and R-warfarin enantiomers by using modified HPLC method.

Warfarin is a commonly prescribed anticoagulant existing in two enantiomeric forms S- and R-warfarin. Many techniques have been used to analyze warfarin in plasma but less frequently for enantiomeric analysis. One of the HPLC method employed was further simplified and made economical.

Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods.

Pharmacokinetics of standard dose regimens of rifampicin in patients with pulmonary tuberculosis in Pakistan.

Background: This clinical study investigated the pharmacokinetics of standard doses of rifampicin (RMP; 450 and 600 mg) in pulmonary tuberculosis (TB) patients in the context of its high sterilizing potential and the increased frequency of multidrug-resistant TB in Pakistan. The objective of this study was to determine the sufficiency or inadequacy of peak plasma levels of RMP in pulmonary TB patients after the administration of standard doses.

Methods: Twenty adult patients with newly diagnosed pulmonary TB consented to participate in the study.

Determination of pharmacokinetics of flurbiprofen in Pakistani population using modified HPLC method.

Pharmacokinetics of flurbiprofen has been studied in different populations, especially in Caucasian. However, there are very few studies reported from Eastern part of world. Previous studies suggested that genetic and environmental factors may cause inter-individual differences in flurbiprofen disposition, so we investigated the pharmacokinetics of flurbiprofen in Pakistani subjects.

Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine.

Background: Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers.

Methods: Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study.

Pharmacological basis for use of Pistacia integerrima leaves in hyperuricemia and gout.

Ethnopharmacological Significance: Pistacia integerrima Stew ex. Brandis is an important component of commonly dispensed traditional dosage forms. We wished to determine whether polyphenolic constituents of this plant could be useful in oxidative stress and have potential to counter hyperuricemia.