Synthesis, Characterization and Molecular Docking of New Nucleosides and Schiff Bases Derived from Ampyrone as Antiviral Agents to Contain the COVID-19 Virus

A new series of nucleoside derivatives was prepared from the reaction of 4-aminoantipyrene with different sugar moieties. In addition, ampyrone's reaction with different aromatic aldehydes gave the corresponding Schiff base derivatives, which were also synthesized. Both molecular docking and in vitro antiviral activities at different concentrations of different synthesized compounds against SARS-CoV-2 were screened. All newly synthesized compounds were characterized on the basis of IR, 1H NMR and 13C NMR spectral data and physical data. The compounds were screened for potential cytotoxic activities. The molecular docking analysis showed that compounds 6b, 6e, 6c, 6f and 6d exhibited relatively higher binding energies (−8.1, −8.1, −8.3, −8.4 and −8.7 kcal/mol, respectively) compared to all the other compounds. However, the different compounds did not show any promising in vitro antiviral activities against SARS-CoV-2.

Neuropsychiatric symptoms in post-COVID-19 long haulers.

BACKGROUND: Long haulers have been recently reported after contracting coronavirus disease (COVID-19). In the present study, we aimed to screen for the neuropsychiatric signs detected <1 to >6 months after infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to determine whether vaccination has an effect on them. METHODS: An online survey was conducted among participants who had been diagnosed with laboratory-confirmed SARS-CoV-2 infection. The clinical signs and durations of neuropsychiatric complaints and their correlations to sex, age, severity of COVID-19 signs, and vaccination status were screened. RESULTS: A total of 2218 individuals, including 1358 females and 860 males, with an age range of 12-70 years, submitted their responses. The respondents experienced cognitive dysfunction, mood alteration, depression, tinnitus, sleep disorders, and loss of taste and smell, with prevalence rates ranging from 18.9% (tinnitus) to 63.9% (loss of taste and smell). Of the respondents, 2.2-7.7% confirmed the persistence of symptoms for >6 months. Tinnitus was the least common complaint, and only 2.2% of the study participants had tinnitus for >6 months. Meanwhile, mood alteration persisted for >6 months in 7.6% of the study participants. More respondents who received two doses of BNT162b2 vaccine showed persistent symptoms than those in the other groups. Disease severity and female sex were identified as potential determinants of the development and persistency of such symptoms. CONCLUSION: Post-COVID neuropsychiatric symptoms were present in considerable percentages of the study participants with SARS-CoV-2 infection, persisting for >6 months in up to 7.6% of the participants.

Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.

Menstrual cycle changes: A cross-sectional study of Saudi females following SARS-CoV-2 infection.

Temporary changes in the menstrual cycle have recently been reported following SARS-CoV-2 vaccination. In the current study, we aimed to screen menstrual cycle changes following SARS-CoV-2 infection in Saudi Arabia. The type and duration of these changes have been screened in relation to the severity of coronavirus disease symptoms and vaccination status. In total, 956 individuals responded: sixty-nine did not get the COVID-19 vaccine, while the remaining were vaccinated with either a single dose of ChAdOx1 vaccine (n:45) or BNT162b2 vaccine (n: 142) or two doses of the vaccine (n:700) using BNT162b2 (n:477), ChAdOx1 (n:89) or ChAdOx1/ BNT162b2 (n:134). Approximately 26.1% (18/69) of the subjects who did not receive the SARS-CoV-2 vaccine and 15.3% (29/188) and 26.4% (185/700) of the subjects who received single and double doses of the vaccines, respectively, reported menstrual cycle changes. The persistence of menstrual cycle changes for more than six months was reported by 6.4% (61/956) of the participants. These changes were significantly correlated with the severity of COVID-19 infection. We concluded that menstrual cycle changes, associated with COVID-19 infection, increase due to the severity of COVID-19 infection. Thus, menstrual cycle changes are among the long-term effects associated with COVID-19 infection.

Tracing the origin of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A systematic review and narrative synthesis.

The aim of the study was to trace and understand the origin of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through various available literatures and accessible databases. Although the world enters the third year of the coronavirus disease 2019 pandemic, health and socioeconomic impacts continue to mount, the origin and mechanisms of spill-over of the SARS-CoV-2 into humans remain elusive. Therefore, a systematic review of the literature was performed that showcased the integrated information obtained through manual searches, digital databases (PubMed, CINAHL, and MEDLINE) searches, and searches from legitimate publications (1966-2022), followed by meta-analysis. Our systematic analysis data proposed three postulated hypotheses concerning the origin of the SARS-CoV-2, which include zoonotic origin (Z), laboratory origin (L), and obscure origin (O). Despite the fact that the zoonotic origin for SARS-CoV-2 has not been conclusively identified to date, our data suggest a zoonotic origin, in contrast to some alternative concepts, including the probability of a laboratory incident or leak. Our data exhibit that zoonotic origin (Z) has higher evidence-based support as compared to laboratory origin (L). Importantly, based on all the studies included, we generated the forest plot with 95% confidence intervals (CIs) of the risk ratio estimates. Our meta-analysis further supports the zoonotic origin of SARS/SARS-CoV-2 in the included studies.

Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study.

Like most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities to both the cell receptor and the drugs targeting such a protein. The current study intended to assess the ability of different variants of interest (VOIs) and variants of concern (VOCs) of SARS-CoV-2 for their affinities of binding to different repurposed drugs. Seven FDA approved drugs, namely, camostat, nafamostat mesylate, fenofibrate, umifenovir, nelfinavir, cefoperazone and ceftazidime, were selected based on their reported in vitro and clinical activities against SARA-CoV-2. The S1 protein subunit from eleven different variants, including the latest highly contiguous omicron variant, were used as targets for the docking study. The docking results revealed that all tested drugs possess moderate to high binding energies to the receptor-binding domain (RBD) of the S1 protein for all different variants. Cefoperazone was found to possess the highest binding energy to the RBD of the S1 protein of all the eleven variants. Ceftazidime was the second-best drug in terms of binding affinity towards the S1 RBD of the investigated variants. On the other hand, fenofibrate showed the least binding affinity towards the RBD of the S1 protein of all eleven variants. The binding affinities of anti-spike drugs varied among different variants. Most of the interacting amino acid residues of the receptor fall within the RBD (438-506).

Laboratory biomarker predictors for disease progression and outcome among Egyptian COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in more than five hundred million infected cases worldwide. The current study aimed to screen the correlation of different laboratory findings with disease severity and clinical outcomes of coronavirus disease (COVID-19) among Egyptian patients to obtain prognostic indicators of disease severity and outcome.A total of 112 laboratory-confirmed COVID-19 patients were examined. According to the severity of the disease, these patients were divided into three main groups: mild, moderate and severe cases. In addition, clinical characteristics and laboratory findings, including Hb, platelet count, white blood cell count, lymphocyte percentage, neutrophil percentage, neutrophil lymphocyte ratio (NLR), D-dimer, highly sensitive C-reactive protein (HS-CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine, were measured.The presence of hypertension and/or diabetes was found to be a significant risk factor for disease severity and poor outcome. Increased respiratory rate, levels of SpO2, HS-CRP, D-dimer, NLR, ALT, LDH, lymphopenia and neutrophilia, as well as changes in chest computed tomography (CT), were associated with increased disease severity and fatal consequences. Highly sensitive C-reactive protein, D-dimer, NLR and LDH constituted excellent predictors for both disease severity and death.Laboratory biomarkers, such as HS-CRP, D-dimer, NLR and LDH, are excellent predictors for both disease severity and death. They can predict mortality in patients at the time of admission secondary to SARS-CoV-2 infection and can help physicians identify high-risk patients before clinical deterioration.

Clinical manifestations of SARS-CoV-2 infection in neonates and the probability of maternal transmission.

AIM: This study aimed to measure the incidence of SARS-CoV-2 infection in neonates from infected mothers and to screen disease severity in neonates. METHODS: We conducted a population-based cohort study of neonates from SARS-CoV-2-positive mothers, enrolling mothers who tested positive for SARS-CoV-2 and their neonates. Eleven infants <25 days old presenting with SARS-CoV-2 infection were also included in the study. We recorded clinical symptoms of SARS-CoV-2-positive mothers and their neonates. RESULTS: One of 126 babies born to SARS-CoV-2-infected mothers was found to be positive (0.79%). The referred positive neonates were either asymptomatic or suffered from symptoms ranging from mild respiratory distress to pneumonia. Most SARS-CoV-2-positive neonates showed neutropenia and lymphocytosis. Most of the SARS-CoV-2-infected mothers (n = 126) were either asymptomatic (46, 36.5%) or showed mild respiratory distress (66, 52.4%). However, pneumonia and severe respiratory distress were reported in 14 (11.1%) of the SARS-CoV-2-infected mothers. There were no deaths of either SARS-CoV-2-infected mothers or neonates. CONCLUSION: We conclude that mothers transmitted infection to their neonates at a very low rate. Disease in neonates is usually mild, although some babies have severe disease. SARS-CoV-2 infection in late pregnancy usually leads to mild maternal disease, but severe disease is reported in approximately one-tenth of the infected women.

Transmission dynamics and mutational prevalence of the novel Severe acute respiratory syndrome coronavirus-2 Omicron Variant of Concern.

The novel Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant, Omicron (PANGO lineage B.1.1.529) is being reported from all around the world. The WHO has categorized Omicron as a Variant of Concern (VOC) considering its higher transmissibility and infectivity, vaccine breakthrough cases. As of January 6, 2022, Omicron has been reported in at least 149 countries. Therefore, this study was planned to investigate the transmission dynamics and mutational prevalence of the novel SARS-CoV-2 Omicron variant. The transmission dynamics and Omicron SARS-CoV-2 divergence was studied using GISAID and Nextstrain which provides information about the genetic sequences, epidemiological, geographical, and species-specific data of human, avian, and animal viruses. Further, the mutation prevalence in spike glycoprotein of Omicron was studied, and the frequency of the crucial mutations was compared with the other prevalent VOCs. The transmission dynamics suggest that the Omicron was first identified in South Africa and then it was reported in the United Kingdom followed by the United States and Australia. Further, our phylogenetic analysis suggests that Omicron (BA.1) was clustered distinctly from the other VOCs. In the Spike glycoprotein, the Omicron (B.1.1.529) demonstrates critical 32 amino acid changes. This study may help us to understand mutational hotspots, transmission dynamics, phylogenetic divergence, effect on testing and immunity, which shall promote the progress of the clinical application and basic research.

Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) variant of concern and its global perspective.

As the latest identified novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC), the influence of Omicron on our globe grows promptly. Compared with the last VOC (Delta variant), more mutations were identified, which may address the characteristics of Omicron. Considering these crucial mutations and their implications including an increase in transmissibility, COVID-19 severity, and reduction of efficacy of currently available diagnostics, vaccines, and therapeutics, Omicron has been classified as one of the VOC. Notably, 15 of these mutations reside in the receptor-binding domain of spike glycoprotein, which may alter transmissibility, infectivity, neutralizing antibody escape, and vaccine breakthrough cases of COVID-19. Therefore, our present study characterizes the mutational hotspots of the Omicron variant in comparison with the Delta variant of SARS-CoV-2. Furthermore, detailed information was analyzed to characterize the global perspective of Omicron, including transmission dynamic, effect on testing, and immunity, which shall promote the progress of the clinical application and basic research. Collectively, our data suggest that due to continuous variation in the spike glycoprotein sequences, the use of coronavirus-specific attachment inhibitors may not be the current choice of therapy for emerging SARS-CoV-2 VOCs. Hence, we need to proceed with a sense of urgency in this matter.

World Society for Virology first international conference: Tackling global virus epidemics.

This communication summarizes the presentations given at the 1st international conference of the World Society for Virology (WSV) held virtually during 16-18 June 2021, under the theme of tackling global viral epidemics. The purpose of this biennial meeting is to foster international collaborations and address important viral epidemics in different hosts. The first day included two sessions exclusively on SARS-CoV-2 and COVID-19. The other two days included one plenary and three parallel sessions each. Last not least, 16 sessions covered 140 on-demand submitted talks. In total, 270 scientists from 49 countries attended the meeting, including 40 invited keynote speakers.

BNT162b2 and ChAdOx1 SARS-CoV-2 Post-vaccination Side-Effects Among Saudi Vaccinees.

Background: Vaccination against SARS-CoV-2 is important for reducing hospitalization and mortalities. Both Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines are used in Saudi Arabia and in many parts of the world. Post-vaccinal side effects were recorded, so we aimed to screen different complaints after vaccination among vaccinees in Saudi Arabia. Methods: An online questionnaire was designed to screen the local, systemic, and allergic post vaccination reactions for vaccinees who received either one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 vaccine. The number and percentage were recorded for each response and analyzed using cross-tab and Chi square tests. The degree of the severity of post vaccination reactions were analyzed using Roc curve. The cofactors that may affect the severity of post-vaccinal reactions including previous COVID-19 infection, age, sex, body mass index, and comorbidities were investigated. Results: During our study, 4,170 individuals reported their responses: 2,601 received one dose of BNT162b2, of whom 456 completed the second dose, and 1,569 received a single dose of ChAdOx1. The side effects were reported in 85.6% of BNT162b2 vaccinees and 96.05% of ChAdOx1 vaccinees who voluntarily responded to a survey about post-vaccination side effects. The side effects were more severe in BNT162b2 than ChAdOx1. ChAdOx1 vaccinees reported mild, moderate, severe and critical side effects in 30.13, 28.62, 29.73, and 1.53%, respectively. In contrast, mild side effects were recorded among the majority of BNT162b2 vaccinees (63.92%) while moderate, severe, and critical side effects were 27.67, 7.68, and 0.72%, respectively. Both local and systemic side effects were recorded more frequently in ChAdOx1 in comparison to BNT162b2 vaccinees. Palpitation was among the new systemic side effects reported in the current study in high frequency. Abnormal menstrual cycle (delaying/increase hemorrhages or pain) was also reported in 0.98% (18/1846) of Pfizer-BioNTech and 0.68% (7/1028) of ChAdOx1 vaccinees, while deep vein thrombosis was only reported in a single case vaccinated with BNT162b2 vaccine. Conclusion: Both vaccines induced post-vaccinal side effects; however, ChAdOx1 induces a higher frequency of post-vaccinal systemic side effects than BNT162b2.

Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients.

The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBRTM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.

SARS-CoV-2 Spike Protein Extrapolation for COVID Diagnosis and Vaccine Development.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to coronavirus disease 2019 (COVID-19) pandemic affecting nearly 71.2 million humans in more than 191 countries, with more than 1.6 million mortalities as of 12 December, 2020. The spike glycoprotein (S-protein), anchored onto the virus envelope, is the trimer of S-protein comprised of S1 and S2 domains which interacts with host cell receptors and facilitates virus-cell membrane fusion. The S1 domain comprises of a receptor binding domain (RBD) possessing an N-terminal domain and two subdomains (SD1 and SD2). Certain regions of S-protein of SARS-CoV-2 such as S2 domain and fragment of the RBD remain conserved despite the high selection pressure. These conserved regions of the S-protein are extrapolated as the potential target for developing molecular diagnostic techniques. Further, the S-protein acts as an antigenic target for different serological assay platforms for the diagnosis of COVID-19. Virus-specific IgM and IgG antibodies can be used to detect viral proteins in ELISA and lateral flow immunoassays. The S-protein of SARS-CoV-2 has very high sequence similarity to SARS-CoV-1, and the monoclonal antibodies (mAbs) against SARS-CoV-1 cross-react with S-protein of SARS-CoV-2 and neutralize its activity. Furthermore, in vitro studies have demonstrated that polyclonal antibodies targeted against the RBD of S-protein of SARS-CoV-1 can neutralize SARS-CoV-2 thus inhibiting its infectivity in permissive cell lines. Research on coronaviral S-proteins paves the way for the development of vaccines that may prevent SARS-CoV-2 infection and alleviate the current global coronavirus pandemic. However, specific neutralizing mAbs against SARS-CoV-2 are in clinical development. Therefore, neutralizing antibodies targeting SARS-CoV-2 S-protein are promising specific antiviral therapeutics for pre-and post-exposure prophylaxis and treatment of SARS-CoV-2 infection. We hereby review the approaches taken by researchers across the world to use spike gene and S-glycoprotein for the development of effective diagnostics, vaccines and therapeutics against SARA-CoV-2 infection the COVID-19 pandemic.

Clinical and Laboratory Findings of COVID-19 in High-Altitude Inhabitants of Saudi Arabia.

Background: SARS-CoV-2, the causative agent of COVID-19, continues to cause a worldwide pandemic, with more than 147 million being affected globally as of this writing. People's responses to COVID-19 range from asymptomatic to severe, and the disease is sometimes fatal. Its severity is affected by different factors and comorbidities of the infected patients. Living at a high altitude could be another factor that affects the severity of the disease in infected patients. Methods: In the present study, we have analyzed the clinical, laboratory, and radiological findings of COVID-19-infected patients in Taif, a high-altitude region of Saudi Arabia. In addition, we compared matched diseased subjects to those living at sea level. We hypothesized that people living in high-altitude locations are prone to develop a more severe form of COVID-19 than those living at sea level. Results: Age and a high Charlson comorbidity score were associated with increased numbers of intensive care unit (ICU) admissions and mortality among COVID-19 patients. These ICU admissions and fatalities were found mainly in patients with comorbidities. Rates of leukocytosis, neutrophilia, higher D-dimer, ferritin, and highly sensitive C-reactive protein (CRP) were significantly higher in ICU patients. CRP was the most independent of the laboratory biomarkers found to be potential predictors of death. COVID-19 patients who live at higher altitude developed a less severe form of the disease and had a lower mortality rate, in comparison to matched subjects living at sea level. Conclusion: CRP and Charlson comorbidity scores can be considered predictive of disease severity. People living at higher altitudes developed less severe forms of COVID-19 disease than those living at sea level, due to a not-yet-known mechanism.

The prevalence of MERS-CoV among military personnel and their families: A single-center study.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a Betacoronavirus that results in a severe fatal respiratory disease; however, it is also associated with mild inapparent infections. The western part of the Kingdom of Saudi Arabia (KSA) contains the holy places where millions of Muslims gathered from all over the world, all year round, with a high probability of mass disease transmission. The aim of this study was to estimate the prevalence of MERS-CoV among military personnel and their families during the period 2014-2019, in the western part of the KSA. A total of 35,203 sputum samples collected from patients with respiratory distress were screened for the presence of MERS-CoV using real-time reverse-transcription polymerase chain reaction in the examined patients. MERS-CoV infections were detected at a very low percentage in the examined patients. Only 42 of the examined subjects (0.12%) were found positive for MERS-CoV. Most infected cases (32/42) cases were detected in 2014, and the rest of the cases were reported in 2015-2019. The cases with fatal consequences (n = 20) were only detected in 2014. It was concluded that there is a very low prevalence of MERS-CoV infections among the military personnel and their families.

Insights into SARS-CoV-2 evolution, potential antivirals, and vaccines.

SARS-CoV-2 is a novel coronavirus, spread among humans, and to date, more than 100 million of laboratory-confirmed cases have been reported worldwide. The virus demonstrates 96% similarity to a coronavirus from a horseshoe bat and most probably emerged from a spill over from bats or wild animal(s) to humans. Currently, two variants are circulating in the UK and South Africa and spread to many countries around the world. The impact of mutations on virus replication, virulence and transmissibility should be monitored carefully. Current data suggest recurrent infection with SARS-CoV-2 correlated to the level of neutralising antibodies and with sustained memory responses following infection. Recently, remdesivir was FDA approved for treatment of COVID-19, however many potential antivirals are currently in different clinical trials. Clinical data and experimental studies indicated that licenced vaccines are helpful in controlling the disease. However, the current vaccines should be evaluated against the emerging variants of SARS-CoV-2.