Aflatoxin Contamination, Its Impact and Management Strategies: An Updated Review

Aflatoxin, a type of mycotoxin, is mostly produced by Aspergillus flavus and Aspergillus parasiticus. It is responsible for the loss of billions of dollars to the world economy, by contaminating different crops such as cotton, groundnut, maize, and chilies, and causing immense effects on the health of humans and animals. More than eighteen different types of aflatoxins have been reported to date, and among them, aflatoxins B1, B2, G1, and G2 are the most prevalent and lethal. Early detection of fungal infection plays a key role in the control of aflatoxin contamination. Therefore, different methods, including culture, chromatographic techniques, and molecular assays, are used to determine aflatoxin contamination in crops and food products. Many countries have set a maximum limit of aflatoxin contamination (2–20 ppb) in their food and agriculture commodities for human or animal consumption, and the use of different methods to combat this menace is essential. Fungal infection mostly takes place during the pre- and post-harvest stage of crops, and most of the methods to control aflatoxin are employed for the latter phase. Studies have shown that if correct measures are adopted during the crop development phase, aflatoxin contamination can be reduced by a significant level. Currently, the use of bio-pesticides is the intervention employed in many countries, whereby atoxigenic strains competitively reduce the burden of toxigenic strains in the field, thereby helping to mitigate this problem. This updated review on aflatoxins sheds light on the sources of contamination, and the on occurrence, impact, detection techniques, and management strategies, with a special emphasis on bio-pesticides to control aflatoxins.

Recovery time of patients infected from COVID-19 in Pakistan

The present study was aimed to improve the general public understanding of COVID-19 pandemic, current study aims to estimate the recovery time of patients infected from COVID-19. Data for this retrospective study was taken from the Saidu group of teaching hospitals district Swat, Khyber Pakhtunkhwa, Pakistan. The study period was form March 24, 2020, to August 25, 2020. A total of 372 COVID-19 positive cases from March 2020 to August 2020 were included in the study. The entry point of each patient was the date of admission in the hospital and the event of interest was the recovery of a patient from COVID-19. Variable of interest were date of admission, date of discharge, age and gender for all patients. All 372 patients were COVID-19 positive recorded between the first positive to the first negative SARS-CoV-2 PCR test results. The Kaplan Meier estimator was used to obtain the recovery time of patients in days from COVID-19 diagnosis. Present study estimated average time of recovery from COVID-19 in district Swat which was 8 days with 0.95% C.I. (7-9) days. The difference between recovery time for males and females was not significant but the difference between recovery time for age groups was significant using the log-rank test.

Role of remdisivir among COVID-19 patient's recovery

Objective: To assess the effect of Remedisvir, its safety Profile, and efficacy among COVID-19 patients. Study Design: Retrospective Observational study. Setting: South East Hospital and Research Center, Islamabad, Pakistan. Period: December 2020 to July 2021. Material & Methods: 100 patients were included in this study who received Remedisvir infusion, day 5, 7, and 10 after admitting the hospital with COVID-19 symptoms. We infuse 200mg I/V Remedisvir in 100cc N/S followed by 100mg I/V daily into 100cc N/S. After infusion, all patients were monitored strictly. Results: The mean age of the patients was (51. 89±15.441). The outcome of Remedisvir showed that 14% improved their condition, 42% discharged with oxygen, 27% discharged without oxygen, and only 17% expired). Remedisvir showed a positive effect at (p≤0.001) among laboratory values and oxygen support category. Conclusion: When patient suffering from COVID-19 symptoms and low oxygen saturation show good clinical outcome treated with Remedisvir. According to the results of our study, it is concluded that, at present Remedisvir remains a good drug, it shows a positive effect on oxygen saturation and length of hospital stay. [ FROM AUTHOR] Copyright of Professional Medical Journal is the property of Professional Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Delta plus variant with neutral mutation is less virulent compared to wild type SARS-CoV2 (preprint)

Background: With the start of the Coronavirus disease19 (COVID19) pandemic, the Coronavirus has mutated constantly. Recently a new variant called Delta plus has been reported in few countries, including South Africa, Brazil and India. The Delta plus variant contains an additional mutation called K417N on the coronavirus spike. The present study aims to determine the virulence and transmissibility of the Delta plus variant and to check the efficiency of different antibodies on its neutralization. Materials: and Methods Different computational tools such as PROVEAN, an online tool, HOPE server, simulation using CABS Flex, Clus pro, an online docking tool, were used to predict the structure and function of Delta plus variant by performing a comparative study with wild type protein. Also, to find an effective antibody against Delta plus variant, antigen-antibody docking studies were conducted through Clus pro server. Furthermore, we performed a 2D interaction diagram analysis to find the amino acid residue's interaction against antibodies. Results: PROVEAN and HOPE showed the mutation (K417N) in the S-glycoprotein of Delta plus as NEUTRAL mutation. This mutation causes the loss of cysteine bonds leading to the destabilization of the 3D structure of spike protein. Furthermore, the RMSF plot emphasizing the 17 th amino acid position of wild and Delta plus mutant revealed the high fluctuation of mutant protein structure compared to the wild protein structure. Further, a comparative docking study against hACE2 shows higher binding energy of wild-type RBD (-751.7 kcal/mol) than mutant RBD (-750.1 kcal/mol). Moreover, antigen-antibody docking study revealed higher affinity of BD-23 Fab antibodies with greater interaction energy ( -997 kcal/mol) compared to other antibodies and thus may prove to be a promising therapeutic against Delta plus variant. Conclusion: Delta plus variant is less stable, has a lower binding affinity to hACE2 and has less virulence than wild type. However, the BD-23 Fab antibody has shown a more significant association for this variant and can be used in its treatment.

Computational Approach for Covalent Lead Identification against Spike Glycoprotein of SARS-CoV-2 (preprint)

Background: A global outbreak of coronavirus disease 19 (COVID-19) led researchers to investigate various active compounds that can inhibit the replication of SARS-CoV2 (severe acute respiratory syndrome coronavirus 2). The present work targets to evaluate small covalent synthetic molecules through a virtual screening and docking approach that can efficiently inhibit Spike Glycoprotein of SARS CoV2. Methods: We retrieved around 50,000 small covalent synthetic molecules through the American chemical society (CAS) database. The initial evaluation of these synthetic molecules depends on the ADMET screening. A Lipinski's Rule of Five (RO5) was also applied to find whether the drug met the criteria of good bioavailability. Then, the further selection was made through virtual screening using BIOVIA Discovery Studio. Further, comparison among top hits was performed via a docking approach based on the binding energy (kcal/mol) calculated using the AutoDock Vina plugin and Patch Dock-like docking engines. Finally, the selected top five molecules were compared for their binding efficiency with reference drugs like Favipiravir, Chloroquine, Ribavirin, Hydroxychloroquine (approved by the FDA), and molecules with better binding affinity than reference drugs was selected. Results: In the first tier of selection, 215 molecules were screened out, satisfying all the necessary conditions of RO5 and ADMET. Among 215 molecules screened, only 203 molecules were stable in structure to undergo the second tier of target-based virtual screening. Further, based upon the LibDock score generated by virtual screening, the top five molecules with the highest LibD score were selected. Molecular docking of these five selected compounds reveals compound2 (3-ethyl-5-propyladamantan-1-amine) with the best binding energy. Furthermore, we compared the binding affinity of 3-ethyl-5-propyladamantan-1-amine with reported drugs that show 3-ethyl-5-propyladamantan-1-amine as the most promising ligand efficient hydrogen bond interactions with amino acid residues of protein which provides more excellent stability in the docked region of the protein with efficient binding energy as compared to the reference molecule. Moreover, Compound2 also has a high oral bioavailability, non-mutagenicity, non-toxicity and follows all RO5 criteria. Conclusion: Thus, it has potential as an antiviral covalent synthetic molecule that may prevent the replication of spike protein. These findings are just preliminary selection to facilitate the upcoming tests from in vivo and in vitro studies.

Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7 (preprint)

New variants of SARS-CoV-2 are being reported worldwide. More specifically, the variants reported in South Africa (501Y.V2) and United Kingdom (B.1.1.7) were found to be more contagious than the wild type. There are also speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19, occurs through the interaction of receptor binding domain (RBD) of the spike protein with peptidase domain of the human ACE-2 (hACE-2) receptor. So, possibly the mutations in the RBD domain of spike protein in the new variants could modulate the protein-protein interaction with hACE-2 receptor leading to the increased virulence. In this study, we aim to get molecular level understanding into the mechanism behind the increased infection rate due to such mutations in these variants. We have computationally studied the interaction of the spike protein in both wild-type and B.1.1.7 variant with hACE-2 receptor using combined molecular dynamics and binding free energy calculations using molecular mechanics-Generalized Born surface area (MM-GBSA) approach. The binding free energies computed using configurations from minimization run and low temperature simulation show that mutant variant of spike protein has increased binding affinity for hACE-2 receptor (i.e. ΔΔG(N501Y,A570D) is in the range −20.4 to −21.4 kcal/mol)The residue-wise decomposition analysis and intermolecular hydrogen bond analysis evidenced that the N501Y mutation has increased interaction between RBD of spike protein with ACE-2 receptor. We have also carried out calculations using density functional theory and the results evidenced the increased interaction between three pairs of residues (TYR449 (spike)-ASP38 (ACE-2), TYR453-HIE34 and TYR501-LYS353) in the variant that could be attributed to its increased virulence. The free energies of wild-type and mutant variants of the spike protein computed from MM-GBSA approach suggests that latter variant is stable by about −10.4 kcal/mol when compared to wild type suggesting that it will be retained in the evolution due to increased stability. We demonstrate that with the use of the state-of-the art of computational approaches, we can in advance predict the more virulent nature of variants of SARS-CoV-2 and alert the world health-care system.

Kawasaki Disease-Like Features in 10 Pediatric COVID-19 Cases: A Retrospective Study.

Children with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), usually present with symptoms of mild upper respiratory tract infection without developing any significant complications. However, this observation has been rendered incautious by hundreds of clinical cases from around the world that have depicted a less benign multisystem inflammatory illness mimicking Kawasaki disease in COVID-positive pediatric patients. Our study aimed at retrospectively reviewing the different features of Kawasaki disease-like illness in children suffering from COVID-19, including the complications, laboratory investigations, treatment strategies used during their hospital stay, and outcomes. We searched the electronic database of the two pediatric units of Mayo Hospital, Lahore, Pakistan, for children who had been admitted to the ward between April 2020 and July 2020 and were diagnosed with COVID-19. A total of 10 such pediatric cases were found, whose clinical details were then reviewed and the obtained data were presented in the form of tables and percentages. The median age was between 4 months to 11 years (mean: 6 years). Of the 10 patients, 8 (80%) were boys. Criteria for Kawasaki disease were met in all of them (100%), with a complete presentation in five (50%). Fever (100%), conjunctival and oral cavity changes (90%), and rash (80%) were the most common features. Seven (70%) patients required admission to a critical care unit, but no mortality occurred. This article can assist in understanding and dealing with Kawasaki disease-like manifestation of pediatric COVID-19 infection, especially in critical care settings, and its possible complications. It will help in a timely and appropriate decision-making regarding treatment and management of such cases.

Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment.

Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. A total of six species have been identified to cause disease in humans. They are known to infect the neurological, respiratory, enteric, and hepatic systems. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome related coronavirus (SARS-CoV). Yet again, we see the emergence of another outbreak due to a new strain called the SARS-CoV-2 virus. The most recent outbreak initially presented as pneumonia of unknown etiology in a cluster of patients in Wuhan, China. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. This review will introduce a general overview of coronavirus and describe the clinical features, evaluation, and treatment of COVID-19 patients. It will also provide a means to raise awareness among primary and secondary healthcare providers during the current pandemic. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling of patients worldwide.