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Background: Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection., Methods: A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection., Results: A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%-78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%)., Conclusion: Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects., Trial Registration: NCT06170320 (retrospectively registered on December 21, 2023)., (© 2024. The Author(s).)

COVID-19, a disease caused by the SARS-CoV-2 virus, is responsible for a pandemic since March 2020 and it has no cure. Therefore, herein, different theoretical methods were used to obtain potential candidates from herbal compounds to inhibit the SARS-CoV-2 main protease (M pro ). Initially, the 16 best-scored compounds were selected from a library containing 4066 ligands using virtual screening by molecular docking. Among them, six molecules (physalin B 5,6-epoxide (PHY), methyl amentoflavone (MAM), withaphysalin C (WPC), daphnoline or trilobamine (TRI), cepharanoline (CEP) and tetrandrine (TET)) were selected based on Lipinski's rule and ADMET analysis as criteria. These compounds complexed with the M pro were submitted to triplicate 100   ns molecular dynamics simulations. RMSD, RMSF, and radius of gyration results show that the overall protein structure is preserved along the simulation time. The average ΔG binding values, calculated by the MM/PBSA method, were -41.7, -55.8, -45.2, -38.7, -49.3, and -57.9   kcal/mol for the PHY-M pro , MAM-M pro , WPC-M pro , CEP-M pro , TRI-M pro , and TET-M pro complexes, respectively. Pairwise decomposition analyses revealed that the binding pocket is formed by His41-Val42, Met165-Glu166-Leu167, Asp187, and Gln189. The PLS regression model generated by QSPR analysis indicated that non-polar and polar groups with the presence of hydrogen bond acceptors play an important role in the herbal compounds-M pro interactions. Overall, we found six potential candidates to inhibit the SARS-CoV-2 M pro and highlighted key residues from the binding pocket that can be used for future drug design. Communicated by Ramaswamy H. Sarma.

The healthy immune system eliminates pathogens and maintains tissue homeostasis through extraordinarily complex networks with feedback systems while avoiding potentially massive tissue destruction. Many parameters influence humoral and cellular vaccine responses, including intrinsic and extrinsic, environmental, and behavioral, nutritional, perinatal and administrative parameters. The relative contributions of persisting antibodies and immune memory as well as the determinants of immune memory induction, to protect against specific diseases are the main parameters of long-term vaccine efficacy. Natural and vaccine-induced immunity and monoclonal antibody immunotherapeutic, may be evaded by SARS-CoV-2 variants. Besides the complications of the production of COVID-19 vaccinations, there is no effective single treatment against COVID-19. However, administration of a combined treatment at different stages of COVID-19 infection may offer some cure assistance. Combination treatment of antiviral drugs and immunomodulatory drugs may reduce inflammation in critical COVID-19 patients with cytokine release syndrome. Molnupiravir, remdesivir and paxlovid are the approved antiviral agents that may reduce the recovery time. In addition, immunomodulatory drugs such as lactoferrin and monoclonal antibodies are used to control inflammatory responses in their respective auto-immune conditions. Therefore, the widespread occurrence of highly transmissible variants like Delta and Omicron indicates that there is still a lot of work to be done in designing efficient vaccines and medicines for COVID-19. In this review, we briefly discussed the immunological response against SARS-CoV-2 and the vaccines approved by the World Health Organization (WHO) for COVID-19, their mechanisms, and side effects. Moreover, we mentioned various treatment trials and strategies for COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Molecular docking of 234 unique compounds identified in the softwood bark (W set) is presented with a focus on their inhibition potential to the main protease of the SARS-CoV-2 virus 3CL pro (6WQF). The docking results are compared with the docking results of 866 COVID19-related compounds (S set). Furthermore, machine learning (ML) prediction of docking scores of the W set is presented using the S set trained TensorFlow, XGBoost, and SchNetPack ML approaches. Docking scores are evaluated with the Autodock 4.2.6 software. Four compounds in the W set achieve a docking score below -13 kcal/mol, with (+)-lariciresinol 9'-p-coumarate (CID 11497085) achieving the best docking score (-15 kcal/mol) within the W and S sets. In addition, 50% of W set docking scores are found below -8 kcal/mol and 25% below -10 kcal/mol. Therefore, the compounds identified in the softwood bark, show potential for antiviral activity upon extraction or further derivatization. The W set molecular docking studies are validated by means of molecular dynamics (five best compounds). The solubility (Log S, ESOL) and druglikeness of the best docking compounds in S and W sets are compared to evaluate the pharmacological potential of compounds identified in softwood bark., (Copyright © 2022. Published by Elsevier B.V.)

We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3' position. Monofatty acyl conjugates, 3'-O-tetradecanoyl (4a) (IC 50(VeroE6)  = 2.3 μM; IC 50(Calu3)  = 0.24 μM), 3'-O-4-oxatetradodecanoyl (4b) (IC 50(VeroE6)  = 2.0 μM; IC 50(Calu3)  = 0.18 μM), and 3'-O-(12-ethylthiododecanoyl) (4e) (IC 50(VeroE6)  = 2.4 μM; IC 50(Calu3)  = 0.25 μM) derivatives exhibited less activity than RDV (IC 50(VeroE6)  = 0.85 μM; IC 50(Calu3)  = 0.06 μM) in both VeroE6 and Calu3 cells. Difatty acylation led to a significant reduction in the antiviral activity of RDV (as shown in conjugates 5a and 5b) against SARS-CoV-2 when compared with monofatty acylation (3a-e and 4a-e). About 77.9% of 4c remained intact after 4 h incubation with human plasma while only 47% of parent RDV was observed at the 2 h time point. The results clearly indicate the effectiveness of fatty acylation to improve the half-life of RDV. The antiviral activities of a number of monofatty acyl conjugates of RDV, such as 3b, 3e, and 4b, were comparable with RDV against the Ebola trVLP system. Meanwhile, the corresponding physical mixtures of RDV and fatty acids 6a and 6b showed 1.6 to 2.2 times less antiviral activity than the corresponding conjugates, 4a and 4c, respectively, against SARS-CoV-2 in VeroE6 cells. A significant reduction in viral RNA synthesis was observed for selected compounds 3a and 4b consistent with the IC 50 results. These studies indicate the potential of these compounds as long-acting antiviral agents or prodrugs of RDV., Competing Interests: Declaration of competing interest The increasing prevalence of COVID-19 is a severe public health problem affecting people globally. COVID-19 is taking a devastating toll on human lives. Several existing drugs and potential drug candidates such as remdesivir (RDV) have been considered for repurposing as COVID-19 treatments. Our group has previously studied the impact of fatty acylation on the antiviral activity of different anti-HIV (human immunodeficiency virus) nucleoside drugs. The conjugates were more potent and less toxic than their parent nucleoside analogs, providing a much higher selectivity index. Furthermore, the conjugates significantly enhanced the cellular uptake versus the parent analogs and corresponding physical mixtures of fatty acids and nucleosides. Herein, we report the synthesis of fatty acyl derivatives of RDV and structural characterization of their antiviral activity against SARS-CoV-2 in VeroE6 cells and Calu3 cells. Five fatty acids, myristic acid, 12-azidododecanoic acid, 12-thioethyldodecanoic acid, 4-oxatetradecanoic acid, and palmitic acid were conjugated to RDV at its 2′-O- and 3′-O-position. Most monofatty acyl derivatives of RDV demonstrated IC(50) values against SARS-CoV-2 that were only slightly decreased relative to RDV. Against the EBOV trVLP and infectious EBOV, any of the monofatty acyl conjugates had IC(50)s similar to that of RDV. Overall, these data together indicate that RDV can be modified with fatty acids at positions 2′ or 3′, without demonstrating a significant loss of antiviral activity in cell culture against SARS-CoV-2 and EBOV. Future studies will determine if these modifications result in greater long-acting effect, bioavailability, and stability in animal models., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Abstract Background Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection. Methods A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection. Results A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%–78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%). Conclusion Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects. Trial registration NCT06170320 (retrospectively registered on December 21, 2023).