Background: Quercetin, a well-known naturally occurring polyphenol, has recently been shown by molecular docking, in vitro and in vivo studies to be a possible anti-COVID-19 candidate. Quercetin has strong antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties, and it is characterized by a very high safety profile, exerted in animals and in humans. Like most other polyphenols, quercetin shows a very low rate of oral absorption and its clinical use is considered by most of modest utility. Quercetin in a delivery-food grade system with sunflower phospholipids (Quercetin Phytosome ® , QP) increases its oral absorption up to 20-fold. Methods: In the present prospective, randomized, controlled, and open-label study, a daily dose of 1000 mg of QP was investigated for 30 days in 152 COVID-19 outpatients to disclose its adjuvant effect in treating the early symptoms and in preventing the severe outcomes of the disease. Results:The results revealed a reduction in frequency and length of hospitalization, in need of non-invasive oxygen therapy, in progression to intensive care units and in number of deaths. The results also confirmed the very high safety profile of quercetin and suggested possible anti-fatigue and pro-appetite properties. Conclusion: QP is a safe agent and in combination with standard care, when used in early stage of viral infection, could aid in improving the early symptoms and help in preventing the severity of COVID-19 disease. It is suggested that a double-blind, placebo-controlled study should be urgently carried out to confirm the results of our study.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic pathogen capable of causing severe respiratory disease in humans. Although dromedary camels are considered as a major reservoir host, the MERS-CoV infection dynamics in camels are not fully understood. Through surveillance in Pakistan, nasal (n = 776) and serum (n = 1050) samples were collected from camels between November 2015 and February 2018. Samples were collected from animal markets, free-roaming herds and abattoirs. An in-house ELISA was developed to detect IgG against MERS-CoV. A total of 794 camels were found seropositive for MERS-CoV. Prevalence increased with the age and the highest seroprevalence was recorded in camels aged [ 10 years (81.37%) followed by those aged 3.1-10 years (78.65%) and B 3 years (58.19%). Higher prevalence was observed in female (78.13%) as compared to male (70.70%). Of the camel nasal swabs, 22 were found to be positive by RT-qPCR though with high Ct values. Moreover, 2,409 human serum samples were also collected from four provinces of Pakistan during 2016-2017. Among the sampled population, 840 humans were camel herders. Although we found a high rate of MERS-CoV antibody positive dromedaries (75.62%) in Pakistan, no neutralizing antibodies were detected in humans with and without contact to camels.

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Worldwide antiretroviral therapy (ART) has reduced the mortality and morbidity rates in individuals with HIV infection. However, the increasing occurrence of drug resistance is limiting treatment options. In recent years, Pakistan has witnessed a concentrated epidemic of HIV. It is very important to identify geographical linkages and mutations that generate selective pressure and drive resistance of HIV in our population. The aim of this work was to identify genetic diversity and drug resistance patterns of HIV in Pakistan, using available sequences and bioinformatics tools, which may help in selecting effective combination of available drugs. A total of 755 Pakistani HIV gag, pol and env sequences were retrieved from the Los Alamos HIV database. Sequences were aligned with reference sequences of different subtypes. For geographical linkages, sequences of predominant subtypes were aligned with sequences of the same subtypes from different countries. Phylogenetic trees were constructed using the maximum-likelihood method in MEGA 7 software. For drug resistance analysis, sequences were entered into the Stanford University HIV Drug Resistance Database. Phylogenetic trees for studying genetic diversity showed that 82% of the sequences were of subtype A, while the rest of the sequences were of subtypes B (9.5%), K (2%), D (2%) and AE (1%). Moreover, trees that were constructed to examine geographical linkages showed close clustering of strains with those of the neighboring countries Afghanistan and India, as well as some African countries. A search for drug resistance mutations showed that 93% of the sequences had no major or minor mutations. The remaining 7% of the sequences contained a major mutation, Y115F, which causes the virus to exhibit low to intermediate resistance against lamivudine and emtricitabine. Our data indicate that HIV subtype A is the major subtype, while subtypes K, D and AE are also present in our country, suggesting gradual viral evolution and possible entry of different subtypes from neighboring countries. These data suggest that HIV is still sensitive to most of the antiretroviral drugs used in Pakistan.

BackgroundCongenital afibrinogenemia (OMIM #202400) is a rare coagulation disorder that was first described in 1920. It is transmitted as an autosomal recessive trait that is characterized by absent levels of fibrinogen (factor I) in plasma. Consanguinity in Pakistan and its neighboring countries has resulted in a higher number of cases of congenital fibrinogen deficiency in their respective populations. This study focused on the detection of mutations in fibrinogen genes using DNA sequencing and molecular modeling of missense mutations in all three genes [Fibrinogen gene alpha (FGA), beta (FGB) and gamma (FGG)] in Pakistani patients.MethodsThis descriptive and cross sectional study was conducted in Karachi and Lahore and fully complied with the Declaration of Helsinki. Patients with fibrinogen deficiency were screened for mutations in the Fibrinogen alpha (FGA), beta (FGB) and gamma (FGG) genes by direct sequencing. Molecular modeling was performed to predict the putative structure functional impact of the missense mutations identified in this study.ResultsTen patients had mutations in FGA followed by three mutations in FGB and three mutations in FGG, respectively. Twelve of these mutations were novel. The missense mutations were predicted to result in a loss of stability because they break ordered regions and cause clashes in the hydrophobic core of the protein.ConclusionsCongenital afibrinogenemia is a rapidly growing problem in regions where consanguinity is frequently practiced. This study illustrates that mutations in FGA are relatively more common in Pakistani patients and molecular modeling of the missense mutations has shown damaging protein structures which has profounding effect on phenotypic bleeding manifestations in these patients.