Study on potential common action and mechanism of Reduning Injection against SARS, MERS and COVID-19 based on network pharmacology and molecular docking technology.

Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.

A Review on the Effect of COVID-19 in Pregnant Women

Coronavirus Disease 2019 (COVID-19) is an emerging disease with a rapid increase in cases and deaths since its first discovery in December 2019, in Wuhan, China. Limited data are available on COVID-19 effects during pregnancy;however, information on diseases associated with other highly pathogenic coronaviruses (i.e. Severe Acute Respiratory Syndrome [SARS] and the Middle East respiratory syndrome [MERS]) may provide insight into the effects of COVID-19 during pregnancy. Coronaviruses cause illnesses ranging from the common cold to severe respiratory disease and death. The data indicate an average of 5 days incubation period (range: 2-14 days). The average age range of the hospitalized patients was 49-56 years, and a third to half of them have an underlying illness. Children were rarely mentioned. Within hospitalized cases, men were more frequent (54%-73%). Fever, cough, myalgia, vomiting, and diarrhea are common symptoms. This review aims at giving an in-depth understanding of COVID-19 by comparing its effects with SARS and MERS to evaluate its severity in pregnant women1. The results of varied studies show that COVID-19 affects pregnant women seriously and there is an alarming need to look into this aspect to prevent its harmful effects on the fetus.Copyright © 2020

Convalescent plasma transfusion in severe or critically ill COVID 19 patients: a rapid systematic review

Currently, there is no availability of any proven specific treatment or prevention strategy to fight against COVID-19. Convalescent plasma (CP) therapy is expected to increase survival rates in COVID-19 as in the case of emerging viral infection (SARS-CoV and MERS-CoV). To collect all the studies relevant to CP therapy in critically ill or severe COVID-19 patients and summarize the findings. The systematic review was conducted according to the PRISMA consensus statement. A systematic search was performed in PubMed, Scopus, Web of Science, and Cochrane databases on April 25, 2020. A total of six studies (28 patients) relevant to CP therapy in severe or critical COVID-19 are considered for inclusion. Two authors extracted the data about study characteristics, demographics, symptoms, co-morbidities, clinical classification of COVID-19, drug therapies, oxygen therapy, laboratory results, chest CT, neutralizing antibody titer, SARS-CoV-2 RNA load, aal outcome. The review findings revealed that CP therapy increases lymphocyte count, reduced s serum inflammatory markers (CRP, IL-6, Procalcitonin) and liver enzyme levels (AST or ALT). There was a rise in serum neutralizing antibody titers in 10 of 14 patients after CP transfusion. In 4 of 14 patients, the titer levels remain unchanged after CP transfusion. All 28 cases (100%) achieved negative to the SARS-CoV-2 RNA after CP transfusion. The convalescent plasma transfusion can improve neutralizing antibody titers and reduces the viral load in severe/critical COVID-19 patients. The review recommends a well-controlled trial design is required to give a definite statement on the safety and efficacy of convalescent plasma therapy in severe/critical COVID-19.

Perceptions of Frontline Healthcare Professionals on Covid-19 Vaccination

Emerging infectious diseases (EIDs) and their determinants are attracting increasing attention from scientists, with approximately 75% of EIDs being zoonotic. Among these pathogens are viruses belonging to the Coronaviridae family. Until 2002, CoVs were primarily studied for scientific or veterinary purposes. However, the world's view on the virulence of CoVs changed in 2002 when a zoonotic betacoronavirus named SARS-CoV appeared in southern China and caused a global epidemic with over 8,000 cases. Ten years later, in the Middle East, another zoonotic betacoronavirus, MERS-CoV, emerged and caused 2,521 cases. A new highly contagious CoV named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in 2019, causing the largest pandemic of the modern era known as coronavirus disease 2019 (COVID-19). Vaccination is one of the most effective methods to reduce the risk of severe illness, hospitalization, and death. The main objective of the study was to evaluate the acceptability of the COVID-19 vaccine among healthcare workers, describe the main adverse reactions, and identify the need for medication administration based on the severity of the adverse reactions manifested.Copyright © 2023, Romanian Society for Pharmaceutical Sciences. All rights reserved.

Historical perspective: other human coronavirus infectious diseases, SARS and MERS

Alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1) are common causes of upper respiratory tract infection in humans. SARS-CoV-1 and MERS-CoV emerged in 2002 and 2012, respectively, with the potential of causing severe and lethal disease in humans, termed SARS and MERS, respectively. Bats appear to be the common natural source of SARS-like coronaviruses including SARS-CoV-1, but their role in MERS-CoV is less clear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV, respectively. Nosocomial outbreaks are hallmarks of SARS and MERS. MERS patients with comorbidities or immunosuppression tend to progress more rapidly to respiratory failure and have a higher case fatality rate than SARS patients. SARS has disappeared since 2004, while there are still sporadic cases of MERS in the Middle East. Continued global surveillance is essential for SARS-like coronaviruses and MERS-CoV to monitor changing epidemiology due to viral variants.Copyright © ERS 2021.

Human coronaviruses in the 'One Health' context

Seven human coronaviruses have been identified so far: four seasonal coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) and three novel coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2). While seasonal coronaviruses cause only mild symptoms, novel coronaviruses cause severe and potentially fatal infections. All known coronaviruses originated in animals. Bats are considered as an origin for the majority of coronaviruses capable of infecting humans;however, rodents are proposed as natural hosts for HCoV-OC43 and HCoV-HKU1. Different animal species could serve as intermediate hosts including alpacas (HCoV-229E), livestock (HCoV-OC43), civet cats (SARS-CoV), camels (MERS-CoV), and pangolins (SARS-CoV-2). In Croatia, SARS-CoV-2 was detected in humans, pet animals, wildlife, and the environment. The COVID-19 pandemic has highlighted the role of the 'One Health' approach in the surveillance of zoonotic diseases.Copyright © 2022, University Hospital of Infectious Diseases. All rights reserved.

MERS-CoV‒Specific T-Cell Responses in Camels after Single MVA-MERS-S Vaccination.

We developed an ELISPOT assay for evaluating Middle East respiratory syndrome coronavirus (MERS-CoV)‒specific T-cell responses in dromedary camels. After single modified vaccinia virus Ankara-MERS-S vaccination, seropositive camels showed increased levels of MERS-CoV‒specific T cells and antibodies, indicating suitability of camel vaccinations in disease-endemic areas as a promising approach to control infection.

Outbreaks of different viral etiologies amidst COVID-19 pandemic

The COVID-19 pandemic has severely affected public health system and surveillance of other communicable diseases across the globe. The lockdown, travel constraints and COVID phobia turned down the number of people with illness visiting to the clinics or hospitals. Besides this, the heavy workload of SARS-CoV-2 diagnosis has led to the reduction in differential diagnosis of other diseases. Consequently, it added to the underlying burden of many diseases which remained under-diagnosed. Amidst the pandemic, the rise of emerging and re-emerging infectious diseases was observed worldwide and reported to the World Health Organization i.e., Crimean Congo Hemorrhagic Fever (2022, Iraq;2021 India), Nipah virus (2021, India), Zika virus (2021, India), and H5N1 influenza (2021, India), Monkeypox (2022, multicountry outbreak), Ebola virus disease (2022, DRC, Uganda;2021, DRC, Guinea;2020, DRC), Marburg (2022, Ghana;2021, Guinea), Yellow fever (2022, Uganda, Kenya, West and Central Africa;2021, Ghana, Venezuela, Nigeria;2020, Senegal, Guinea, Nigeria, Gabon;2020, Ethiopia, Sudan, Uganda), Dengue (2022, Nepal, Pakistan, Sao Tome, Temor-Leste;2021, Pakistan), Middle east respiratory syndrome coronavirus (2022, Oman, Qatar;2021, Saudi Arabia, UAE;2020, Saudi Arabia, UAE), Rift valley fever (2021, Kenya;2020, Mauritania), wild poliovirus type 1 (2022, Mozambique), Lassa fever (2022, Guinea, Togo, Nigeria;2020, Nigeria), Avian Influenza (H3N8) (2022, China), Avian Influenza (H5N1) (2022, USA), H10N3 influenza (2021, China), Hepatitis E virus (2022, Sudan), Measles (2022, Malawi, Afghanistan;2020, Burundi, Mexico), Mayaro virus disease (2020, French Guiana), Oropouche virus disease (2020, French Guiana). All these diseases were associated with high morbidity and burdened the public health system during the COVID-19 pandemic. During this critical public health menace, majority of the laboratory workforce was mobilized to the SARS-CoV-2 diagnosis. This has limited the surveillance efforts that likely led to under diagnosis and under-detection of many infectious pathogens. Lockdowns and travel limitations also put a hold on human and animal surveillance studies to assess the prevalence of these zoonotic viruses. In addition, lack of supplies and laboratory personnel and an overburdened workforce negatively impacted differential diagnosis of the diseases. This is especially critical given the common symptoms between COVID-19 and other pathogens causing respiratory illnesses. Additionally, the vaccination programs against various vaccine preventable diseases were also hampered which might have added to the disease burden. Despite these challenges, the world is better prepared to detect and respond to emerging/re-emerging pathogens. India now has more than 3000 COVID-19 diagnostic laboratories and an enhanced hospital infrastructure. In addition, mobile BSL-3 facilities are being validated for onsite sampling and testing in remote areas during outbreak situations and surveillance activities. This will undoubtedly be valuable as the COVID-19 pandemic evolves as well as during future outbreaks and epidemics. In conclusion, an increase in the emergence and re-emergence of viruses demonstrates that other infectious diseases have been neglected during the COVID-19 pandemic. Lessons learned from the infrastructure strengthening, collaborations with multiple stakeholders, increased laboratory and manufacturing capacity, large-scale COVID-19 surveillance, extensive network for laboratory diagnosis, and intervention strategies can be implemented to provide quick, concerted responses against the future threats associated with other zoonotic pathogens.

SARS-CoV-2 ANTIVIRAL ACTIVITY OF ZOTATIFIN, A HOST-TARGETING eIF4A INHIBITOR

Background: Zotatifin (eFT226) is a potent and selective inhibitor of eukaryotic initiation factor 4A (eIF4A), a host RNA helicase required for SARS-CoV-2 replication. Zotatifin selectively inhibits translation of ribonucleic acids (RNAs) containing specific short polypurine motifs in their 5-prime (5') regions. Two such highly conserved motifs are found in the SARS-CoV-2 genome. Zotatifin is currently being evaluated in a Phase 1b dose escalation study in 36 patients with mild to moderate COVID disease. In this in vitro study, we evaluated the selectivity of zotatifin's inhibition of SARS-CoV-2 translation, the antiviral activity of zotatifin alone against different human coronaviruses and the antiviral activity of zotatifin in combination with other antivirals against SARSCoV-2. Method(s): The selectivity of zotatifin for viral translation was evaluated in a cell-based reporter assay wherein luciferase translation was driven by 5'-sequences from SARS-CoV-2 or tubulin, a housekeeping gene. The antiviral activity of zotatifin was evaluated against SARS-CoV-1, SARS-CoV-2 variants (Wash/1/2020 (ancestral), delta, omicron BA.2), MERS-CoV and HCoV-299E in primary or established cell lines using cytopathic effect or infectious virus as endpoints. The antiviral activity of zotatifin in combination with remdesivir, N-hydroxycytidine (NHC;active nucleoside analogue metabolite of molnupiravir), nirmatrelvir, baricitinib or sotrovimab was evaluated against SARS-CoV-2 and analyzed by the method of Pritchard and Shipman. Result(s): Zotatifin inhibited the translation of the SARS-CoV-2 luciferase reporter construct with a mean IC50 of 3 nM and was ~14-fold less potent in inhibiting the tubulin reporter construct. Zotatifin potently inhibited the replication of all human coronaviruses tested with 50% effective concentrations (EC50s) ranging from 0.016 to 37.3 nM. The 50% cytotoxic concentration (CC50) value for zotatifin was 250 to >100,000 nM, yielding selectivity indices of 7 to >6250. Zotatifin was ~20 to >100-fold more potent than remdesivir, nirmatrelvir or NHC (figure) and demonstrated additive interactions when combined with remdesivir, NHC, nirmatrelvir, baricitinib or sotrovimab in vitro. Conclusion(s): The potent broad-spectrum activity of zotatifin against a variety of human coronaviruses and additive activity when combined with different anti-SARS-CoV-2 antivirals highlight the advantages of eIF4A as a target and warrant further evaluation in human clinical trials.

PHASE 1 CLINICAL TRIALS OF A Q-GRIFFITHSIN NASAL SPRAY FOR SARS-CoV-2 PROPHYLAXIS

Background: The currently approved vaccines do not induce sterilizing immunity against SAR-CoV-2 infection, and immunity wanes over time. A robust broad spectrum topical prophylaxis strategy could protect vulnerable populations in the face of continuous evolution of SARS-CoV-2. The algal antiviral lectin Griffithsin (GRFT), and an engineered oxidation-resistant variant Q-GRFT have robust entry inhibitory activity against SARS-CoV variants of concern, in addition to other respiratory viruses with pandemic potential. We designed a nasal spray to deliver Q-GRFT to the upper respiratory tract mucosa for on-demand use as a broad-spectrum prophylactic. Two clinical trials (Phase 1a and 1b) were conducted to assess safety, tolerability, and pharmacokinetics of Q-GRFT nasal spray in healthy adults. Method(s): Healthy adult volunteers were enrolled in a Phase 1a double blinded, randomized study to receive a single dose of either intranasal Q-GRFT (3.0 mg, 2 sprays per nostril) or placebo at 2:1 ratio. Following a safety review, the Phase 1b study was initiated. Eleven volunteers in Group 1 received 3.0 mg dose once daily, for 7 days. After a safety review, 11 volunteers in Group 2 received a total of 6.0 mg Q-GRFT (3.0 mg twice daily for 7 days). Topical Q-GRFT concentrations were measured by ELISA in collected nasal and nasopharyngeal fluids. Drug levels in plasma were assayed to determine systemic exposure. Viral microneutralization cytopathic effect (CPE) assays were performed against SARS-CoV-2 Omicron BA-5 and MERS-CoV. Result(s): Eighteen adults (24-54 years;Males 58.3%, Females 41.7%;12 Q-GRFT, 6 Placebo), and 22 adults (aged 23-59 years;Males 52.4%, Females 47.6%) were enrolled in Phase 1a and 1b, respectively. In Phase 1a, a single dose of Q-GRFT maintained quantifiable levels in nasal passages and nasopharynx for up to 24 hours. Similarly, Q-GRFT was quantifiable in nasal and nasopharyngeal regions in the Phase 1b study. No dose accumulation effect or systemic exposure was observed. Nasal and nasopharyngeal swab eluates inhibited SARS-CoV-2 Omicron BA.5 and MERS-CoV in CPE assays. Q-GRFT did not modify olfactory sensation. No severe adverse events were reported. Thus, the nasal spray was deemed safe. Conclusion(s): Intranasal Q-GRFT was safe and enhanced mucosal SARSCoV-2 inhibitory activity in human volunteers. The results support further development of Q-GRFT as a broad-spectrum prophylactic against coronaviruses to curb ongoing infections, and for future pandemic preparedness.

Longitudinal Coronavirus Antibody Responses in Africa between 2013 and 2021

Background: Pre-existing coronavirus-specific antibody responses may affect SARS-CoV-2 responses. We evaluated longitudinal samples obtained before and during the pandemic in participants from Kenya, Nigeria, Tanzania and Uganda;90% were people living with HIV. Method(s): Serum samples were tested using a multiplex bead-based immunoassay to measure antibody binding against 22 antigens including Nucleocapsid (N) and Spike (S) proteins of the 7 human coronaviruses and one malaria antigen. Result(s): We tested 819 longitudinal samples from 80 participants collected between July 2013 and May 2021 (3-16 samples per participant). Using a signal to noise ratio (S/N) >10, 13, 1, and 5 participants showed at least one time point with IgG responses to S of SARS-CoV-2 (ancestral), SARS-CoV-1 and MERS-CoV respectively while 14, 8, and 11 participants showed responses to N before 2020. Across individuals, IgG binding to SARS-CoV-2 S subunit S2 was most frequently detected and it showed the highest within-host fluctuations over time. A few individuals had elevated responses that persisted over years towards multiple antigens, most frequently to different SARS-CoV-2 antigens and rarely to distinct viruses. One individual showed high RBD-specific IgG responses to distinct coronaviruses at a single time point before 2020. Responses against coronaviruses measured post-2020 generally correlated with responses measured before 2020, except for a subset of infected individuals whose responses against SARS-CoV-2 dramatically increased post-pandemic. IgG responses against the ancestral SARS-CoV-2 variant were most correlated with responses against Alpha and Gamma (then to Beta and Delta, rho >0.75) variants. Using an IgM S/N >10, 31 participants were Malaria positive and 22 showed concurrent elevated coronavirus IgM responses. However, about half of the malaria positive participants had no IgG responses against any coronavirus antigen and the rest presented limited and variable patterns of association between responses against coronaviruses and malaria. Conclusion(s): Our study confirmed that a small subset of individuals in Africa had long-lasting IgG coronavirus-specific antibodies before the pandemic. While there was an association between coronavirus IgM responses and responses against malaria, there was no correlation between IgG responses and malaria infection. Further analysis is needed to better understand the interactions between antigens in the development of antibody immunity to coronaviruses. (Table Presented).

Establishment of multi-target rapid detection method of upper repiratory susceptible viruses based on digital microfluidic technology

Objective: Provide a digital microfluidic RT-qPCR chip for rapid detection of several upper respiratory diseases. Methods: Several specific primer-probe sets were designed according to the conserved sequences of 2019 novel corona virus(2019-n COV), influenza A virus(Flu A), influenza B virus(Flu B), severe acute respiratory syndrome corona virus(SARS-Co V), Middle East respiratory syndrome corona virus(MERS-Co V), and then packaged into a digital microfluidic chip which allowed simultaneous detection of five upper respiratory tract pathogens with the help of reverse transcription quantitative PCR(RT-q PCR)technology. In the meanwhile, the detection limit, specificity and sensitivity of this digital microfluidic chip were evaluated base on the clinical specimens, plasmids and unrelated pathogens. Results: The established digital microfluidic RT-q PCR chip for 2019-n COV, Flu A, Flu B,SARS-Co V,MERS-Co V had a detection limit of 12 copies/reaction, while the detection limit of the RT-q PCR method without digital microfluidics was 15 copy/reaction;the detection limit of the two methods was basically the same. For nucleic acid samples extracted from clinical samples, the detection results of digital microfluidic RT-q PCR chips were all negative without non-specific amplification. At the same time, the RT-qPCR method and the digital microfluidic RT-qPCR chip method were used to carry out clinical comparative tests of 5 items in 20 clinical samples, total 100 tests. The results showed that the sensitivity of the digital microfluidic RT-q PCR chip reached 94%, the specificity was 100%. SPSS was used to analyze the consistency of the two methods, and the results showed that the two methods had a high degree of consistency(Kappa=0.962, P<0.05). Conclusion: Based on digital microfluidic RT-q PCR chip technology,a multi-target rapid detection method of upper respiratory tract susceptible virus was established, which could provide a new detection method for early clinical identification of respiratory pathogens.

RNA-sequencing unravels unique host-response to infection with SARS-CoV-2

Introduction/Aim: As the causative agent of COVID-19, SARS-CoV-2 remains a global cause for concern. Compared to other highly pathogenic coronaviruses (SARS-CoV and MERS-CoV), SARS-CoV-2 exhibits stronger transmissibility but less lethality, indicating that SARS-CoV-2 displays unique characteristics, despite the partial genomic proximity. Thus, we aim to employ RNA sequencing to define transcriptional differences in epithelial responses following infection with SARS-CoV-2 compared to pathogenic SARS-CoV and MERS-CoV, and low pathogenic HCoV-229E. Method(s): Primary human bronchial epithelial cells (PBEC) were differentiated for 6 weeks at the air-liquid interface (ALI) before parallel infection by the 4 different coronaviruses (n = 4). After infection following apical application of coronaviruses at low dose (MOI 0.1), cells were harvested for bulk RNA sequencing. Gene were considered significant with a fold change (FC) > 2 and false discovery rate of FDR < 0.05. Inhibitor experiments were conducted on CALU-3 cells using DIM-C-pPhOH 10 muM (NR4A1 antagonist), Sp600125 10 muM (JNK inhibitor), T-5224 10 muM (AP-1 transcription factor inhibitor) and Cytosporone B (CsB 5 muM;NR4A1 agonist) preincubated for 1 h with these compounds and subsequently infected with SARS-CoV-2 or MERS-CoV (MOI of 1). Samples were collect 24 h later for PCR. Result(s): PCR and RNA-Seq demonstrated that all tested coronaviruses efficiently infected ALI-PBEC and replicated over 72 h (p < 0.05). RNA sequencing analysis revealed that infection with SARS-CoV, MERS-CoV and HCoV-229E resulted in largely similar transcriptional responses by the epithelial cells. However, whereas infection with these viruses was accompanied by an increased expression of genes associated with JNK/AP-1 signalling, including FOS, FOSB and NR4A1 (FC > 1, FDR < 0.05), no such increase was observed following SARS-CoV-2 infection. Further, we found that an NR4A1 antagonist reduced viral replication of MERS and SARs-CoV-2 100-fold in Calu-3 cells. Conclusion(s): In conclusion, these data suggest that SARS-CoV-2-infected ALI-PBEC exhibit a unique transcriptional response compared to other coronaviruses, which might relate to the pathogenicity of the virus.

SARS-CoV-2 USES ENDOSOMAL MEMBRANES TO BUILD REPLICATION ORGANELLES

Background: The health emergency caused by the COVID-19 pandemic has evidenced that the frequency of spillover episodes of viruses infecting bats to other species, including humans, has significantly increased compared to previous decades. Besides SARS-CoV-2, six other human coronaviruses (NL63, 229E, OC43, HKU1, SARS-CoV and MERS-CoV) emerged in the 20th and 21st century, most likely because of cross-species transmission events from bats. While many of these coronaviruses cause mild respiratory infections, MERS-CoV, SARS-CoV and SARS-CoV-2 can cause severe respiratory distress, particularly in immunocompromised individuals. However, unlike SARS-CoV and MERS-CoV, SARS-CoV-2 is highly contagious, very stable, with many person-to-person transmissions, which can occur even before individuals exhibit any symptoms. While vaccines are readily available, the emergence of new SARS-CoV-2 variants along with the increasing incidence of individuals developing long COVID urge to develop antivirals specific to treat COVID-19. To reach this goal, we need to have a working knowledge of the host-SARS-CoV-2 interactions to identify targets for therapeutic intervention. Method(s): Following that rationale, we focused on understanding how SARSCoV- 2 generates replication organelles (ROs). All coronaviruses need to remodel cellular membranes to create these structures to allow the active replication and transcription of their genome. Due to their relevance for virus replication, disabling RO formation represents a promising strategy to fight SARS-CoV-2. However, the biogenesis mechanism, the origin, and type of these replication organelles are still a major focus of debate. To identify the cellular membranes that SARS-CoV-2 uses to generate ROs we used multiple cell lines and primary cells that were evaluated by fluorescence microscopy, genetic engineering, compounds that specifically inhibit cellular processes, and immunoprecipitation assays to validate protein-protein interactions. We also used RT-qPCR to assess viral genome replication. Result(s): SARS-CoV-2 uses the viral protein NSP6 to remodel endosomal membranes juxtaposed to the ER to generate replication organelles. Specifically, the virus depends on Clathrin, COPB1, and Rab5 for efficient SARSCoV- 2 RNA synthesis. Conclusion(s): Uncovering the origins and mechanism(s) by which SARS-CoV-2 assembles ROs opens new avenues to develop strategies to interfere with RO biogenesis and halt virus replication.

Safety application of novel coronavirus pneumonia antiviral drugs.

Three antiviral drugs, including interferon alpha (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People's Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug-remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.Copyright © 2020 by the Chinese Medical Association.

Medicinal Plants used Traditionally in Sudan to Treat Viral Infections Related to the Signs and Symptoms of COVID-19: A Systematic Review

Background: The rapid global spread of the COVID-19 pandemic urged scientists to search for effective and safe anti-coronavirus drugs from natural resources. Through centuries, traditional medicinal plants have been providing cure for diseases and general health care worldwide. Objective(s): The main aim of this review was to explore and summarize the research works on the different plants used traditionally in Sudan to treat signs and symptoms of COVID-19 and respiratory diseases, characterizing their antiviral activities and exploring the different phytochemicals present in these plants. Method(s): The current review was carried out in line with the recommendations of the PRISMA 2020 statement. Information on plants traditionally used in Sudan to treat the signs and symptoms of COVID-19 and respiratory diseases was obtained from traditional medicine books and published articles, as well as the daily practice by ordinary people. Result(s): This article illustrated the use of 27 plant species belonging to 15 families in Sudanese traditional medicine to treat signs and symptoms of COVID-19 and respiratory diseases. Legumi-nosae/Fabaceae was found to be the most represented family (7 species), followed by Combretaceae (3 species) and Capparidaceae and Malvaceae (2 species each). From these plants, about 11 plant species were studied for their antiviral activity against at least one virus, and 5 plants, namely Adan-sonia digitata, Boscia senegalensis, Hibiscus sabdariffa, Nigella sativa, and Mangifera indica, were tested for their antiviral activity against influenza viruses. The phytoconstituents of the listed plants were summarized, and the antiviral activity of their isolated bioactive compounds was highlighted. Conclusion(s): The review could provide an in-depth theoretical basis and valuable data for designing future studies.Copyright © 2023 Bentham Science Publishers.

Humoral response against SARS-CoV-2 and other endemic corona viruses

In a study of two Hospitals in Saxony (Chemnitz and Leipzig), we analyzed the antibody development towards SARS-CoV-2 and against a variety of endemic coronaviruses. Here we analyzed 760 sera from a Saxonian cohort for antibody reactivity against: Common cold coronaviruses, HCoV-229E, HCoV-HKU 1, HCoV-NL63 and HCoV-OC43, MERS-CoV and SARS-CoV. For the SARS CoV-2 immune response we tested the following antigens: Spike, S1, S2, RBD and nucleocapsid. These 11 antigen determinants were tested in a commercial multiplex Luminex based assay. We tested sera from 544 individuals (347 females and 197 males;498 SARS-CoV-2 PCR positive and 262 SARS-CoV-2 PCR negative) between May 2020 and March 2022. We observed up to 10% reactivity against the MERS virus in both the PCR positive and negative group. Against the common cold corona viruses 80%-90 % of the individuals in both groups show detectable antibodies. Regarding the antibody response against SARS-CoV a significant difference was observe. Only 19% of COVID-19 infected individuals show antibodies against the virus, while 81% of the PCR-positive individuals produced antibodies. The presence of antibodies against the SARS-CoV-2 is positively correlated with those against SARS-CoV (p = 0.001). No changes in endemic antibody responses were see in the two groups. The antibody status after first immunization event (infection/ vaccination) shows differences in nucleocapsiddirected antibody production, found in the natural infection group (about 60%). In the vaccination group, more individuals (up to 95%) show an immune response against Spike, S1 and RBD compare with natural infection. In summary, the examined cohort shows a general immunization up to 90% against most endemic corona viruses. Correlation analyses show cross-reactivity between SARS-CoV-2 and SARS-CoV. Longitudinal antibody analyses are under way, as also correlations of humoral response with immunogenetic factors.

SARS-CoV-2: Molecular Biology and Therapeutic Targets

A century after the outbreak of the Spanish flu, the world is suffering from another pandemic because of the coronavirus. The virus took a toll on more than millions of lives worldwide and continues to affect the health and socio-economic infrastructure all over the world. This study explores the epidemiology, etiology, and transmission of the virus and its phylogenetic relationship with SARS and MERS coronavirus responsible for the 2002 and 2012 viral outbreak. Furthermore, this review highlights the key features of the viral genome and essential viral proteins responsible for the viral life cycle, evading host immune response, and viral immunopathology with therapeutics from "Recovery" and "Solidarity" trials. The review culminates with a discussion on different classes of prominent vaccines and their efficacy. An overall understanding of essential viral proteins and their role in pathogenesis, repurposed drugs, and vaccine development is the rationale of the present review.Copyright © 2021 Bentham Science Publishers.

An Overview of the Treatment Contributions Measured Globally for the COVID-19 Outbreak

Background: SARS CoV2 is a newly emerged animal beta coronavirus that causes respiratory illness. This infection has affected 212 countries to date and has been declared a pandemic by the World Health Organization. Due to the high transmission rate and lack of availability of any approved anti-viral drug, the formulation of a specific anti-viral therapy has now become a global emergency. Genomic studies have revealed a 79% identity of SARS CoV2 with SARS CoV and 50% identity with MERS CoV, which has given a clue point to test the drugs that were efficient against previously encoun-tered beta coronaviruses. For this purpose, several clinical trials based on the knowledge of existing drugs are moving ahead. These therapies include chloroquine and hydroxychloroquine, remdesivir, cor-ticosteroids therapy, favipiravir, ribavirin, lopinavir/ritonavir, anti-cytokine therapy, and convalescent sera. Aim of the study: The purpose of this review is to give a pointer of contributions conducted globally, including strategies utilized for treatments, the pattern of dosage, adverse reactions, and effective outcomes from different drugs. Methodology: Literature has been retrieved from PubMed, PubMed Central, ResearchGate, ScienceDi-rect, and Google Scholar, using a combination of keywords for extensive information. Conclusion(s): Among all the drug options, Remdesivir and the use of Convalescent Sera have been con-sidered as the safest options for treatment against COVID-19. Data from the ongoing clinical trials will be required for the formulation of a specific and approved anti-viral drug,.Copyright © 2021 Bentham Science Publishers.

Development of broadly reactive antibody therapeutics for SARS-CoV-2.

Various antibody therapeutics has been developed for the treatment and suppression of the 2019 outbreak of novel coronavirusSARS-CoV-2infection. A major limitation in the development DDS of SARS-CoV-2 neutralizing antibodies is the occurrence and spread of escape variants that have mutations in the spike glycoprotein. The coronaviruses are carried by various wild animals, domestic animals, and pets, and there have been cases of Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission from animals to people, resulting in a large spread of infection in people. There is also a possibility that cross-species transmission of SARS-CoV-2 may occur in the future. Considering these factors, the development of antibody therapeutics with broad cross-reactivity against SARS-CoV-2 variants and other coronaviruses is required.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.