Identification of inhibitors of the RdRp and Mpro enzymes of SARS-CoV-2 virus by structural homology

TCOVID-19 has enormously impacted global public health due to the high infection and mortality rates associated with the SARS-CoV-2 virus-causing disease. The World Health Organization (WHO) approved 10 safe and effective vaccines. However, there are still significant limitations to their administration in developing countries and remote locations. Concerns remain about the emergence of virus variants that may evade immunity acquired through vaccination. In addition to preventing infection, effective therapeutic agents are needed to treat patients diagnosed with COVID-19. Under this context, the present study aimed to perform a structure-based virtual screening of the protease (Mpro) and RNA-dependent RNA polymerase (RdRp) enzymes of SARS-CoV-2. For this purpose, homologous protein inhibitors belonging to different viruses were tested. Multiple sequence alignment of these enzymes allowed us to recognize the high conservation of these enzymes between species, especially of the regions comprising the inhibitor binding sites. Therefore, it follows that it is possible to employ a redirection approach to inhibitors that were designed to treat other viral diseases. Molecular docking experiments identified that RTP inhibitors (binding affinity = -7.3 kcal/mol) and V3D (binding affinity = -8.0 kcal/mol) are excellent inhibitors of RdRp and Mpro, respectively. These results suggest that these molecules can virtually bind and inhibit the activity of RdRp and Mpro and thus constitute potential drugs to combat SARS-CoV-2. © 2022 by the authors.

COVID-19 impact: a case study at the school of agricultural engineering and environment of the Universitat Politecnica de Valencia

To study the first impact of the COVID-19 crisis on the results obtained by students belonging to the School of Agricultural Engineering and Environment at the Universitat Politecnica de Valencia (Spain), the average of the marks corresponding to three academic years (2016-2019) was compared to those obtained in 2019-2020 for a total of four bachelor's degrees and two semesters. Our results suggest a positive effect on the marks obtained during the activation of emergency remote teaching during the spring semester of 2019-2020 in three out of the four degrees, with these differences being significant for the whole study. Moreover, just at the end of that period, instructors and students were surveyed regarding teaching methodologies, evaluation modalities, and difficulties found throughout the process of adapting to distance teaching. Our results allow us to sensibly think about that exceptional situation in order to propose a set of counterweighting measures which could improve the implementation of distance learning in engineering colleges.

Gianotti-Crosti syndrome related to SARS-COV-2 infection in an infant. Clinical case report

Dermatological manifestations are a frequent sign in the course of covid-19, Gianotti-Crosti syndrome has being observed as a manifestation after sars-cov-2 infection, and should be considered as a possible differential diagnosis. We present the case of an 11-month-old male, who goes to the emergency room with fever of 39.9 °C, is diagnosed as pharyngitis and is discharged home;two weeks later, he went to reassessment due to a maculopapular rash predominantly on the trunk, extremities, anterior and posterior chest, respecting the soles and palms, it was classified as a febrile exanthematous disease. In the context of a covid-19 pandemic, a rapid antigen test was taken with a non-reactive result and serologies for sars-cov-2 igg positive.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial.

BACKGROUND: COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. STUDY DESIGN AND METHODS: This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.