Preisolation measures and clinical features for pediatric patients with suspicious COVID-19.

Background: In December 2019, many cases of COVID-19 were reported in Wuhan City, Hubei Province, China. In the following 3 months, the disease out broke in China. Preisolation measures was used to screen out COVID-19 patients in the pediatric respiratory ward of our hospital. Aims: To investigate the new measures for screening COVID-19 patients and to analyze the clinical features of children with suspicious COVID-19. Methods: A total of 50 preisolated children with suspicious COVID-19 who were admitted to our hospital in Mianyang, China, between January 28 and March 5, 2020, were included. Patients presented with fever and cough or fever accompanied by vomiting and diarrhea. A detailed epidemiological history screening was performed. A real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) was used to detect SARS-COV-2 nucleic acid. Low-dose chest computed tomography (CT) was applied when pneumonia was suspicious. Routine blood tests were performed to rule out COVID-19. Patients' data were collected, and the basic clinical features, epidemiological history, clinical manifestations, auxiliary examination results, and outcomes were analyzed and summarized. Results: No definite cases were detected, while two patients were suspected of having COVID-19. The pathogenic results of the 50 patients mainly included Mycoplasma pneumoniae, followed by Epstein-Barr virus, and rotavirus. Thirty-five patients suffered from bronchopneumonia. The preisolated patients had similar clinical and epidemiological characteristics as patients with fever, cough, vomiting, and diarrhea. Conclusions: Preisolation measures combined with pathogen screening can minimize the risk of hospital-acquired infections by preventing patients with suspicious COVID-19 from contacting other patients before they are explicitly excluded. Clinical analysis of the patients was helpful for clinical nursing management.

Application of weighted gene co-expression network and immune infiltration for explorations of key genes in the brain of elderly COVID-19 patients.

Introduction: Although many studies have demonstrated the existing neurological symptoms in COVID-19 patients, the mechanisms are not clear until now. This study aimed to figure out the critical molecular and immune infiltration situations in the brain of elderly COVID-19 patients. Methods: GSE188847 was used for the differential analysis, WGCNA, and immune infiltration analysis. We also performed GO, KEGG, GSEA, and GSVA for the enrich analysis. Results: 266 DEGs, obtained from the brain samples of COVID-19 and non-COVID-19 patients whose ages were over 70 years old, were identified. GO and KEGG analysis revealed the enrichment in synapse and neuroactive ligand-receptor interaction in COVID-19 patients. Further analysis found that asthma and immune system signal pathways were significant changes based on GSEA and GSVA. Immune infiltration analysis demonstrated the imbalance of CD8+ T cells, neutrophils, and HLA. The MEpurple module genes were the most significantly different relative to COVID-19. Finally, RPS29, S100A10, and TIMP1 were the critical genes attributed to the progress of brain damage. Conclusion: RPS29, S100A10, and TIMP1 were the critical genes in the brain pathology of COVID-19 in elderly patients. Our research has revealed a new mechanism and a potential therapeutic target.

One-Step Synthesis of Self-Stratification Core-Shell Latex for Antimicrobial Coating.

Herein, we describe a one-step method for synthesizing cationic acrylate-based core-shell latex (CACS latex), which is used to prepare architectural coatings with excellent antimicrobial properties. Firstly, a polymerizable water-soluble quaternary ammonium salt (QAS-BN) was synthesized using 2-(Dimethylamine) ethyl methacrylate (DMAEMA) and benzyl bromide by the Hoffman alkylation reaction. Then QAS-BN, butyl acrylate (BA), methyl methacrylate (MMA), and vinyltriethoxysilane (VTES) as reactants and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA) as a water-soluble initiator were used to synthesize the CACS latex. The effect of the QAS-BN dosage on the properties of the emulsion and latex film was systematically investigated. The TGA results showed that using QAS-BN reduced the latex film's initial degradation temperature but improved its thermal stability. In the transmission electron microscopy (TEM) photographs, the self-stratification of latex particles with a high dosage of QAS-BN was observed, forming a core-shell structure of latex particles. The DSC, TGA, XPS, SEM, and performance tests confirmed the core-shell structure of the latex particles. The relationship between the formation of the core-shell structure and the content of QAS-BN was proved. The formation of the core-shell structure was due to the preferential reaction of water-soluble monomers in the aqueous phase, which led to the aggregation of hydrophilic groups, resulting in the formation of soft-core and hard-shell latex particles. However, the water resistance of the films formed by CACS latex was greatly reduced. We introduced a p-chloromethyl styrene and n-hexane diamine (p-CMS/EDA) crosslinking system, effectively improving the water resistance in this study. Finally, the antimicrobial coating was prepared with a CACS emulsion of 7 wt.% QAS-BN and 2 wt.% p-CMS/EDA. The antibacterial activity rates of this antimicrobial coating against E. coli and S. aureus were 99.99%. The antiviral activity rates against H3N2, HCoV-229E, and EV71 were 99.4%, 99.2%, and 97.9%, respectively. This study provides a novel idea for the morphological design of latex particles. A new architectural coating with broad-spectrum antimicrobial properties was obtained, which has important public health and safety applications.

Influence of fear of COVID-19 on depression: The mediating effects of anxiety and the moderating effects of perceived social support and stress perception.

Objective: Explore the influence of fear of COVID-19 on depression, with anxiety as a mediator and perceived social support and stress perception as moderates. Methods: From February to March 2020, 1,196 valid data were collected online through questionnaire by cluster sampling method. Fear of COVID-19 Questionnaire, the Patient Health Questionnaire 9-Item Scale (PHQ-9), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Perceived Social Support Scale (PSSS) and the10-item Perceived Stress Scale (PSS-10) were used as the survey instrument, and the participants were female undergraduates from a liberal arts college of a Chinese university. Common method bias was assessed using Harman's single-factor test in SPSS and confirmatory factor analysis in AMOS. The levels of participants' anxiety, depression and perceived social support were described using frequency and percentage, Pearson Correlation test was used to measure the correlation between the variables. The PROCESS macro for SPSS (Model 1, Model 4, and Model 21) were applied to examine the mediating effect and moderating effect of the model. Results: Fear of COVID-19 can positively influence depression, anxiety plays a mediating role between fear of COVID-19 and depression, perceived social support negatively moderates the relationship between fear of COVID-19 and anxiety, and stress perception positively moderates the relationship between anxiety and depression. These five variables can form a moderated mediating effect model. Conclusion: Fear of COVID-19, anxiety and stress perception are risk factors for depression, perceived social support is a protective factor for depression. Reducing the fear of COVID-19, anxiety and stress perception and enhancing perceived social support are beneficial to reduce the level of depression.

SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.

The coronavirus disease 2019 (COVID-19) pandemic has devastated global health. Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks. Here, we have identified host proteins that associate with nonstructural protein 12 (nsp12), the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 using a mass spectrometry (MS)-based proteomic approach. Among the candidate factors, CDK2 (Cyclin-dependent kinase 2), a member of cyclin-dependent kinases, interacts with nsp12 and causes its phosphorylation at T20, thus facilitating the assembly of the RdRp complex consisting of nsp12, nsp7 and nsp8 and promoting efficient synthesis of viral RNA. The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection. Taken together, we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex, thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors.

Influence of fear of COVID-19 on depression: The mediating effects of anxiety and the moderating effects of perceived social support and stress perception

Objective Explore the influence of fear of COVID-19 on depression, with anxiety as a mediator and perceived social support and stress perception as moderates. Methods From February to March 2020, 1,196 valid data were collected online through questionnaire by cluster sampling method. Fear of COVID-19 Questionnaire, the Patient Health Questionnaire 9-Item Scale (PHQ-9), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Perceived Social Support Scale (PSSS) and the10-item Perceived Stress Scale (PSS-10) were used as the survey instrument, and the participants were female undergraduates from a liberal arts college of a Chinese university. Common method bias was assessed using Harman's single-factor test in SPSS and confirmatory factor analysis in AMOS. The levels of participants' anxiety, depression and perceived social support were described using frequency and percentage, Pearson Correlation test was used to measure the correlation between the variables. The PROCESS macro for SPSS (Model 1, Model 4, and Model 21) were applied to examine the mediating effect and moderating effect of the model. Results Fear of COVID-19 can positively influence depression, anxiety plays a mediating role between fear of COVID-19 and depression, perceived social support negatively moderates the relationship between fear of COVID-19 and anxiety, and stress perception positively moderates the relationship between anxiety and depression. These five variables can form a moderated mediating effect model. Conclusion Fear of COVID-19, anxiety and stress perception are risk factors for depression, perceived social support is a protective factor for depression. Reducing the fear of COVID-19, anxiety and stress perception and enhancing perceived social support are beneficial to reduce the level of depression.

Evaluation of pharmacist-led telemedicine medication management for hypertension established patients during COVID-19 pandemic: A pilot study.

Aim: To evaluate the impact of a telemedicine medication management service in patients with hypertension. Methods: Participants were allocated to either a telemedicine service (N = 173) or usual care (UC) (N = 179). The primary outcome was blood pressure (BP) reduction from baseline to the 6-month follow-up visit, the proportion of the target BP achievement, overall adherence to prescribed medication as well as a composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death. Results: At 6 months, BP was controlled in 89.6% (n = 155) of intervention patients and 78.8% (n = 141) of UC patients (OR = 1.14, 95% CI = 1.04-1.25, P = 0.006), giving a mean difference of -6.0 (-13.0 to -2.5 mmHg) and -2.0 mmHg (-4.0 to -0.1 mmHg) in SBP and DBP, respectively. 17.9% (n = 31) of the patients in the intervention group were non-adherent with medications, compared with 29.1% (n = 52) in the UC group (P = 0.014). The composite clinical endpoints were reached by 2.9% in the intervention group and 4.5% in the control group with no significant differences (OR = 1.566, 95% CI = 0.528-4.646). Conclusion: Telemedicine medication management for hypertension management had led to better BP control and medication adherence improvement than UC during COVID-19 epidemic, resulting in a reduction of overall adverse cardiovascular events occurrence.

The Chemical and Pharmacological Research Progress on a Kind of Chinese Herbal Medicine, Fructus Malvae.

Since the outbreak of the COVID-19 pandemic, traditional Chinese medicine has played an important role in the treatment process. Furthermore, the discovery of artemisinin in Artemisia annua has reduced the incidence of malaria all over the world. Therefore, it is becoming urgent and important to establish a novel method of conducting systematic research on Chinese herbal medicine, improving the medicinal utilization value of traditional Chinese medicine and bringing great benefits to human health all over the world. Fructus Malvae, a kind of Chinese herbal medicine which has been recorded in the "Chinese Pharmacopoeia" (2020 edition), refers to the dry, ripe fruits of Malva verticillata L. Recently, some studies have shown that Fructus Malvae exhibits some special pharmacological activities; for example, it has diuretic, anti-diabetes, antioxidant and anti-tumor properties, and it alleviates hair loss. Furthermore, according to the reports, the active ingredients separated and identified from Fructus Malvae contain some very novel compounds such as nortangeretin-8-O-ß-d-glucuronopyranoside and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride, which could be screened as important candidate compounds for diabetes- or tumor-treatment drugs, respectively. Therefore, in this research, we take Fructus Malvae as an example and systematically summarize the chemical constituents and pharmacological activity research progress of it. This review will be helpful in promoting the development and application of Fructus Malvae and will also provide an example for other investigations of traditional Chinese medicine.

Evaluating Public Sentiments of Covid-19 Vaccine Tweets Using Machine Learning Techniques

The quest to create a vaccine for covid-19 has rekindled hope for most people worldwide, with the anticipation that a vaccine breakthrough would be one step closer to the end of the deadly Covid-19. The pandemic has had a bearing on the use of Twitter as a communication medium to reach a wider audience. This study examines Covid-19 vaccine-related discussions, concerns, and Twitter-emerged sentiments about the Covid-19 vaccine rollout program. Natural Language Processing (NLP) techniques were applied to analyze Covid-19 vaccine-related tweets. Our analysis identified popular n-grams and salient themes such as "vaccine health information," "vaccine distribution and administration," "vaccine doses required for immunity," and "vaccine availability." We apply machine learning algorithms and evaluate their performance using the standard metrics, namely accuracy, precision, recall, and f1-score. Support Vector Machine (SVM) classifier proves to be the best fit on the dataset with 84.32% accuracy. The research demonstrates how Twitter data and machine learning methods can study the evolving public discussions and sentiments concerning the Covid-19 vaccine rollout program.

IMO’s Marine Environmental Regulatory Governance and China’s Role: An Empirical Study of China’s Submissions

The International Maritime Organization (IMO) plays a significant role in global marine environmental governance, providing a forum of regulatory oversight for member states. Member states are the main actors of the IMO and exert considerable influence on the process of lawmaking. Among these member states, China is unique due to its multiple identities. There are various factors influencing interests behind China’s multiple identities, which fully engage the country in various shipping and maritime trade activities. This article examines China’s role in the IMO marine environmental regulatory governance. It identifies the impact of China on global ocean governance and indicates the development and reforms in the global governance system. China enacted the China Ocean Agenda 21 for its strategy of ocean development. Thus, China is the object of study in this examination of empirical research that collects submissions from 2001 to 2020 related to marine environmental governance. The findings reveal that the extent to which China participates in such governance has considerably increased, and although the contribution of China’s submissions is still in development, its role in the IMO is no longer merely that of a follower, and the efforts of the country have had a positive influence on the IMO’s marine environmental regulatory governance, including its legal instruments.

5-Iodotubercidin inhibits SARS-CoV-2 RNA synthesis.

Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid global emergence of SARS-CoV-2 highlights the importance and urgency for potential drugs to control the pandemic. The functional importance of RNA-dependent RNA polymerase (RdRp) in the viral life cycle, combined with structural conservation and absence of closely related homologs in humans, makes it an attractive target for designing antiviral drugs. Nucleos(t)ide analogs (NAs) are still the most promising broad-spectrum class of viral RdRp inhibitors. In this study, using our previously developed cell-based SARS-CoV-2 RdRp report system, we screened 134 compounds in the Selleckchemicals NAs library. Four candidate compounds, Fludarabine Phosphate, Fludarabine, 6-Thio-20-Deoxyguanosine (6-Thio-dG), and 5-Iodotubercidin, exhibit remarkable potency in inhibiting SARS-CoV-2 RdRp. Among these four compounds, 5-Iodotubercidin exhibited the strongest inhibition upon SARS-CoV-2 RdRp, and was resistant to viral exoribonuclease activity, thus presenting the best antiviral activity against coronavirus from a different genus. Further study showed that the RdRp inhibitory activity of 5-Iodotubercidin is closely related to its capacity to inhibit adenosine kinase (ADK).

2-((1H-indol-3-yl)thio)-N-phenyl-acetamides: SARS-CoV-2 RNA-dependent RNA polymerase inhibitors.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of Coronavirus Disease 2019 (COVID-19) pandemic. Despite intensive and global efforts to discover and develop novel antiviral therapies, only Remdesivir has been approved as a treatment for COVID-19. Therefore, effective antiviral therapeutics are still urgently needed to combat and halt the pandemic. Viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 demonstrates high potential as a reliable target for the development of antivirals. We previously developed a cell-based assay to assess the efficiency of compounds that target SARS-CoV-2 RdRp, as well as their tolerance to viral exoribonuclease-mediated proof-reading. In our previous study, we discovered that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides specifically targets the RdRp of both respiratory syncytial virus (RSV) and influenza A virus. Thus, we hypothesize that 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides may also have the ability to inhibit SARS-CoV-2 replication by targeting its RdRp activity. In this research, we test a compound library containing 103 of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides against SARS-CoV-2 RdRp, using our cell-based assay. Among these compounds, the top five candidates strongly inhibit SARS-CoV-2 RdRp activity while exhibiting low cytotoxicity and resistance to viral exoribonuclease. Compound 6-72-2a is the most promising candidate with the lowest EC50 value of 1.41 µM and highest selectivity index (CC50/EC50) (above 70.92). Furthermore, our data suggests that 4-46b and 6-72-2a also inhibit the replication of HCoV-OC43 and HCoV-NL63 virus in a dose-dependent manner. Compounds 4-46b and 6-72-2a exhibit EC50 values of 1.13 µM and 0.94 µM, respectively, on HCoV-OC43 viral replication. However, higher concentrations of these compounds are needed to effectively block HCoV-NL63 replication. Together, our findings successfully identified 4-46b and 6-72-2a as promising inhibitors against SARS-CoV-2 RdRp.

COVID-19 vaccination hesitancy and associated factors among solid organ transplant recipients in China.

The mortality rate from COVID-19 appears to be higher in solid organ transplant (SOT) recipients when compared with other populations. Vaccination is a key strategy to prevent the COVID-19 pandemic. However, it is unclear how readily SOT recipients will get vaccinated against COVID-19. We conducted an internet-based survey to investigate the vaccination willingness among Chinese SOT recipients and further explore possible influencing factors. Eight hundred and thirteen respondents participated in the survey. Overall, 46 (5.7%) recipients were vaccinated against COVID-19, while 767 (94.3%) were not. Among those not vaccinated, 175 (22.8%) intended to be vaccinated, while 592 (77.2%) were categorized as vaccine-hesitant. The most common reason for vaccination hesitancy is fear of preexisting comorbidities, followed by fear of side effects and doctors' negative advice. Factors associated with vaccination willingness were as follows: with liver transplantation, the main source of information on COVID-19 vaccines was from medical doctors, scientists, and scientific journals, with at least college-level education, positive intention toward influenza vaccination during the current season, perceived importance of vaccination for SOT recipients, and having been vaccinated against influenza during the last season. Our survey indicated the necessity for SOT recipients to receive more comprehensive and accessible health education about vaccination and emphasized the critical role of transplantation physicians in promoting vaccine acceptance among SOT recipients. We hope that our survey results will help governments to better target communication in the ongoing COVID-19 vaccination campaign.

Stock market reactions to the COVID-19 pandemic: The moderating role of corporate big data strategies based on Word2Vec

By developing a machine learning-based measure of corporate big data strategies, this study empirically explores how stock markets respond to the COVID-19 pandemic and whether corporate big data strategies make firms immune to the pandemic effect. We find that except for information technology and health care sectors, firms in most sectors in China are negatively affected by the COVID-19 outbreak. Among these firms, an increase in the number of daily new confirmed cases in the city of a firm's headquarters is associated with a decrease in its stock prices, however, such a decline is attenuated for firms with a high emphasis on big data strategies. Our results are robust when we use COVID-19 cases at the whole country level.

Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp.

Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.

A cell-based assay to discover inhibitors of SARS-CoV-2 RNA dependent RNA polymerase.

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. In addition, SARS-CoV-2 exoribonuclease provides the proof-reading capacity to viral RdRp, thus creates relatively high resistance threshold of viral RdRp to nucleotide analog inhibitors, which must be examined and evaluated in the development of this class of antivirals. Here, we report a cell-based assay to evaluate the efficacy of nucleotide analog compounds against SARS-CoV-2 RdRp and assess their tolerance to viral exoribonuclease-mediated proof-reading. By testing seven commonly used nucleotide analog viral polymerase inhibitors, Remdesivir, Molnupiravir, Ribavirin, Favipiravir, Penciclovir, Entecavir and Tenofovir, we found that both Molnupiravir and Remdesivir showed the strong inhibition of SARS-CoV-2 RdRp, with EC50 value of 0.22 µM and 0.67 µM, respectively. Moreover, our results suggested that exoribonuclease nsp14 increases resistance of SARS-CoV-2 RdRp to nucleotide analog inhibitors. We also determined that Remdesivir presented the highest resistance to viral exoribonuclease activity in cells. Therefore, we have developed a cell-based SARS-CoV-2 RdRp assay which can be deployed to discover SARS-CoV-2 RdRp inhibitors that are urgently needed to treat COVID-19 patients.

Functional comparison of SARS-CoV-2 with closely related pangolin and bat coronaviruses.

The origin and intermediate host for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is yet to be determined. Coronaviruses found to be closely related to SARS-CoV-2 include RaTG13 derived from bat and two clusters (PCoV-GD and PCoV-GX) of coronaviruses identified in pangolin. Here, we studied the infectivity and antigenicity patterns of SARS-CoV-2 and the three related coronaviruses. Compared with the other three viruses, RaTG13 showed almost no infectivity to a variety of cell lines. The two pangolin coronaviruses and SARS-CoV-2 showed similar infectious activity. However, in SARS-CoV-2-susceptible cell lines, the pangolin coronaviruses presented even higher infectivity. The striking difference between the SARS-CoV-2 and pangolin coronaviruses is that the latter can infect porcine cells, which could be partially attributed to an amino acid difference at the position of 498 of the spike protein. The infection by SARS-CoV-2 was mainly mediated by Furin and TMPRSS2, while PCoV-GD and PCoV-GX mainly depend on Cathepsin L. Extensive cross-neutralization was found between SARS-CoV-2 and PCoV-GD. However, almost no cross-neutralization was observed between PCoV-GX and SARS-CoV-2 or PCoV-GD. More attention should be paid to pangolin coronaviruses and to investigate the possibility of these coronaviruses spreading across species to become zoonoses among pigs or humans.

SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.

The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC50) value of 0.13 µmol/L. Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp. In addition, combination of RAI-S-37 with remdesivir exhibits additive activity against anti-SARS-CoV-2 RdRp. Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent, these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.