Acute kidney disease following COVID-19 vaccination: a single-center retrospective study.

Background: Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination. Methods: This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined. Results: Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5-49.5) weeks, six patients progressed to end-stage kidney disease (ESKD). Conclusion: Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.

Network-based drug repurposing for the treatment of COVID-19 patients in different clinical stages

In the severe acute respiratory coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to develop effective treatments. Through a network-based drug repurposing approach, several effective drug candidates are identified for treating COVID-19 patients in different clinical stages. The proposed approach takes advantage of computational prediction methods by integrating publicly available clinical transcriptome and experimental data. We identify 51 drugs that regulate proteins interacted with SARS-CoV-2 protein through biological pathways against COVID-19, some of which have been experimented in clinical trials. Among the repurposed drug candidates, lovastatin leads to differential gene expression in clinical transcriptome for mild COVID-19 patients, and estradiol cypionate mainly regulates hormone-related biological functions to treat severe COVID-19 patients. Multi-target mechanisms of drug candidates are also explored. Erlotinib targets the viral protein interacted with cytokine and cytokine receptors to affect SARS-CoV-2 attachment and invasion. Lovastatin and testosterone block the angiotensin system to suppress the SARS-CoV-2 infection. In summary, our study has identified effective drug candidates against COVID-19 for patients in different clinical stages and provides comprehensive understanding of potential drug mechanisms.

Network-based drug repurposing for the treatment of COVID-19 patients in different clinical stages.

In the severe acute respiratory coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to develop effective treatments. Through a network-based drug repurposing approach, several effective drug candidates are identified for treating COVID-19 patients in different clinical stages. The proposed approach takes advantage of computational prediction methods by integrating publicly available clinical transcriptome and experimental data. We identify 51 drugs that regulate proteins interacted with SARS-CoV-2 protein through biological pathways against COVID-19, some of which have been experimented in clinical trials. Among the repurposed drug candidates, lovastatin leads to differential gene expression in clinical transcriptome for mild COVID-19 patients, and estradiol cypionate mainly regulates hormone-related biological functions to treat severe COVID-19 patients. Multi-target mechanisms of drug candidates are also explored. Erlotinib targets the viral protein interacted with cytokine and cytokine receptors to affect SARS-CoV-2 attachment and invasion. Lovastatin and testosterone block the angiotensin system to suppress the SARS-CoV-2 infection. In summary, our study has identified effective drug candidates against COVID-19 for patients in different clinical stages and provides comprehensive understanding of potential drug mechanisms.

Anti-DNA-IgM Favors the Detection of NET-Associated Extracellular DNA.

During inflammatory responses, neutrophils enter the sites of attack where they execute various defense mechanisms. They (I) phagocytose microorganisms, (II) degranulate to release cytokines, (III) recruit various immune cells by cell-type specific chemokines, (IV) secrete anti-microbials including lactoferrin, lysozyme, defensins and reactive oxygen species, and (V) release DNA as neutrophil extracellular traps (NETs). The latter originates from mitochondria as well as from decondensed nuclei. This is easily detected in cultured cells by staining of DNA with specific dyes. However, in tissues sections the very high fluorescence signals emitted from the condensed nuclear DNA hamper the detection of the widespread, extranuclear DNA of the NETs. In contrast, when we employ anti-DNA-IgM antibodies, they are unable to penetrate deep into the tightly packed DNA of the nucleus, and we observe a robust signal for the extended DNA patches of the NETs. To validate anti-DNA-IgM, we additionally stained the sections for the NET-markers histone H2B, myeloperoxidase, citrullinated histone H3, and neutrophil elastase. Altogether, we have described a fast one-step procedure for the detection of NETs in tissue sections, which provides new perspectives to characterize neutrophil-associated immune reactions in disease.

Research on the potential mechanism of huashi baidu recipe against nove Coronavirus pneumonia (COVID-19)by network pharmacology and molecular docking technology

Objective:Use network pharmacology to explore the anti-COVID-19 mechanism of Huashi Baidu (HSBD) Recipe, supplemented by molecular docking verification Methods:Thorugh databases such as TCMSP,GeneCard,String, and software such as Cytoscape,AutoDockVina, network relationships was established, and the binding ability of active ingredients and targets is calculated through molecular docking, and biological function enrichment analysis was conducted .

Intensive care unit adaptations in the COVID-19 pandemic: Lessons learned.

The coronavirus disease 2019 pandemic had deleterious effects on the healthcare systems around the world. To increase intensive care units (ICUs) bed capacities, multiple adaptations had to be made to increase surge capacity. In this editorial, we demonstrate the changes made by an ICU of a midwest community hospital in the United States. These changes included moving patients that used to be managed in the ICU to progressive care units, such as patients requiring non-invasive ventilation and high flow nasal cannula, ST-elevation myocardial infarction patients, and post-neurosurgery patients. Additionally, newer tactics were applied to the processes of assessing oxygen supply and demand, patient care rounds, and post-ICU monitoring.

Discussion on the composing principle of "Qingfei paidu decoction" in the treatment of anti-COVID-19 from the theory of syndrome-differentiation of the six meridians in treatise on febrile diseases

The coronavirus disease 2019 (COVID-19) was a newly discovered infectious respiratory disease and characterized by wide prevalence, high incidence rate and fast progress, which belonged to the category of "cold-wet plague" in traditional Chinese medicine. The onset of COVID-19 was caused by pestilence, which mingled with seasonal cold-dampness and invaded the human body when external defensive qi was weak and then leaded to the accumulation of Yang qi. Different from exogenous pathogenic factors transmitted from the external to the internal or followed the transmission law of Wei, Qi, Ying and Xue, the nature of pestilence belonged to the category of pathogenic fire, spreading as soon as possible, from the external to the internal and from the upper and lower part of triple energizer, even to every part. At the very beginning, the pestilence attacked from the Taiyang meridian into the Yangming meridian quickly, or straight into the three Yang meridian, which was called "triple-yang combination of diseases". Manifestations of fever, aversion to cold and pain of body were conformed to the exterior syndrome of Taiyang, as well as manifestations of fullness and discomfort in chest, vomiting and spitting and diarrhea were conformed to the syndrome of half-interior half-exterior;And symptoms manifested as high fever, faint, and abdominal fullness and constipation were conformed to the syndrome of Yangming;But sometimes, there was cold-dampness surrounding the exterior at the beginning along with intense interior pathogenic fire. Or at the beginning, the exterior factors invaded into three Yin meridians quickly while have not been eliminated, which may lead to the syndrome of inner blocking causing collapse or Jue exhaustion. The most typical syndrome of COVID-19 was triple-yang combination of diseases, which was often seen in mild, moderate and part of severe cases. Hence "Qingfei Paidu Decoction" was prescribed especially for this kind of syndrome. Its accurate efficacy has been proved by that mild cases converting to severe cases in the mobile cabin hospital have been effectively restrained and thus the progression of the disease has blocked. Composition analysis showed that Mahuang decoction with Maxing Shigan decoction was to relieve exterior Taiyang syndrome, Xiaochaihu decoction was for harmonizing half-superficies and half-interior Shaoyang syndrome, and large dose of gypsum was used to clear interior heat of the Yangming meridian, and Shegan Mahuang decoction and Xiaoqinglong plus gypsum decoction was for lowering the adverse qi and resolving fluid, and Wuling San was for warming the triple energizer and transforming qi and draining water. "Qingfei Paidu Decoction" was a syncretic innovation of classical prescriptions from Treatise on Febrile Diseases, which was not made up of herbs but multiple concordant prescriptions helping to get twice the result with half the effort, so that the "cold-wet plague" can be quickly discharged.

Ultraminiature optical fiber-tip directly-printed plasmonic biosensors for label-free biodetection.

Miniaturization of biosensors has become an imperative demand because of its great potential in in vivo biomarker detection and disease diagnostics as well as the point-of-care testing for coping with public health crisis, such as the coronavirus disease 2019 pandemic. Here, we present an ultraminiature optical fiber-tip biosensor based on the plasmonic gold nanoparticles (AuNPs) directly printed upon the end face of a standard multimode optical fiber at visible light range. An in-situ precision photoreduction technology is developed to additively print the micropatterns of size-controlled AuNPs. The AuNPs reveal distinct localized surface plasmon resonance, whose peak wavelength provides an ideal spectral signal for label-free biodetection. The fabricated optical fiber-tip plasmonic biosensor can not only detect antibody, but also test SARS-CoV-2 mimetic DNA sequence at the concentration level of 0.8 pM. Such an ultraminiature fiber-tip plasmonic biosensor offers a cost-effective biodetection technology for a myriad of applications ranging from point-of-care testing to in vivo diagnosis of stubborn diseases.

Adverse effect signature extraction and prediction for drugs treating COVID-19.

Given the considerable cost of drug discovery, drug repurposing is becoming attractive as it can effectively shorten the development timeline and reduce the development cost. However, most existing drug-repurposing methods omitted the heterogeneous health conditions of different COVID-19 patients. In this study, we evaluated the adverse effect (AE) profiles of 106 COVID-19 drugs. We extracted four AE signatures to characterize the AE distribution of 106 COVID-19 drugs by non-negative matrix factorization (NMF). By integrating the information from four distinct databases (AE, bioassay, chemical structure, and gene expression information), we predicted the AE profiles of 91 drugs with inadequate AE feedback. For each of the drug clusters, discriminant genes accounting for mechanisms of different AE signatures were identified by sparse linear discriminant analysis. Our findings can be divided into three parts. First, drugs abundant with AE-signature 1 (for example, remdesivir) should be taken with caution for patients with poor liver, renal, or cardiac functions, where the functional genes accumulate in the RHO GTPases Activate NADPH Oxidases pathway. Second, drugs featuring AE-signature 2 (for example, hydroxychloroquine) are unsuitable for patients with vascular disorders, with relevant genes enriched in signal transduction pathways. Third, drugs characterized by AE signatures 3 and 4 have relatively mild AEs. Our study showed that NMF and network-based frameworks contribute to more precise drug recommendations.

Sodium alginate-hydrogel coatings on extracorporeal membrane oxygenation for anticoagulation.

Thromboembolism caused by the use of extracorporeal membrane oxygenation (ECMO) remains common among patients with existing heart diseases and contributes to significant morbidity and mortality during the COVID-19 pandemic. Various surface modification strategies have been proposed, showing that the methacrylated alginate (MA-SA) hydrogel layer is transparent, which aids the observation of the thromboembolism from the inner wall of the tubing. In the combined dynamic and static blood of ECMO tubing inner surface in vitro experiments, it was also demonstrated that the adhesion of blood clots to the surface of vessels was remarkably reduced, and the MA-SA-based hydrogel coating could significantly prolong the activated partial thrombin time and block the endogenous coagulation. The favorable properties of natural polysaccharides of hydrogel coatings make them the best surface material choices to be applied for blood-contacting medical devices and significantly improve anticoagulant performance.

Ultraminiature optical fiber-tip directly-printed plasmonic biosensors for label-free biodetection

Miniaturization of biosensors has become an imperative demand because of its great potential in in vivo biomarker detection and disease diagnostics as well as the point-of-care testing for coping with public health crisis, such as the coronavirus disease 2019 pandemic. Here, we present an ultraminiature optical fiber-tip biosensor based on the plasmonic gold nanoparticles (AuNPs) directly printed upon the end face of a standard multimode optical fiber at visible light range. An in-situ precision photoreduction technology is developed to additively print the micropatterns of size-controlled AuNPs. The AuNPs reveal distinct localized surface plasmon resonance, whose peak wavelength provides an ideal spectral signal for label-free biodetection. The fabricated optical fiber-tip plasmonic biosensor can not only detect antibody, but also test SARS-CoV-2 mimetic DNA sequence at the concentration level of 0.8 pM. Such an ultraminiature fiber-tip plasmonic biosensor offers a cost-effective biodetection technology for a myriad of applications ranging from point-of-care testing to in vivo diagnosis of stubborn diseases.

Effectiveness of Social Video Platforms in Promoting COVID-19 Vaccination Among Youth: A Content-Specific Analysis of COVID-19 Vaccination Topic Videos on Bilibili.

Background: With the widespread promotion of the COVID-19 vaccination in China, videos about the vaccination have become increasingly available on social video platforms. With the User Generated Content model, different creators' interpretations of COVID-19 vaccines may influence the attitudes towards the vaccines and vaccination. Objective: To explore the overview of COVID-19 vaccine-related videos on Bilibili, discussing the communication effects of COVID-19 topic videos and its influencing factors. Methods: A content analysis was applied to the 202 video samples obtained through data mining regarding the creator's information, video presentation, and COVID-19 vaccine-related content. Results: Individuals and medical professionals preferred VLOG videos, media chose to upload informational videos, and enterprises preferred to post showcase videos. Individuals were more likely to discuss the adverse reactions in their videos, while medical professionals were more likely to discuss the vaccination process for the COVID-19 vaccine. Videos with core issues positively influenced the video's dissemination breadth. The attitudes toward the COVID-19 vaccine in the videos positively influence the recognition of the videos. The richness of knowledge points related to the COVID-19 vaccine negatively affected the recognition and participation. Conclusion: Social video platforms could play an active role in the vaccination promotion for the youth. Health promotion-related departments and individuals could strengthen agenda setting, grasp the characteristics of young groups, and express positive attitudes toward health issues to achieve better health (vaccine) promotion.

A panel regression analysis for the COVID-19 epidemic in the United States.

This study explored the roles of epidemic-spread-related behaviors, vaccination status and weather factors during the COVID-19 epidemic in 50 U.S. states since March 2020. Data from March 1, 2020 to February 5, 2022 were incorporated into panel model. The states were clustered by the k-means method. In addition to discussing the whole time period, we also took multiple events nodes into account and analyzed the data in different time periods respectively by panel linear regression method. In addition, influence of cluster grouping and different incubation periods were been discussed. Non-segmented analysis showed the rate of people staying at home and the vaccination dose per capita were significantly negatively correlated with the daily incidence rate, while the number of long-distance trips was positively correlated. Weather indicators also had a negative effect to a certain extent. Most segmental results support the above view. The vaccination dose per capita was unsurprisingly proved to be the most significant factor especially for epidemic dominated by Omicron strains. 7-day was a more robust incubation period with the best model fit while weather had different effects on the epidemic spread in different time period. The implementation of prevention behaviors and the promotion of vaccination may have a successful control effect on COVID-19, including variants' epidemic such as Omicron. The spread of COVID-19 also might be associated with weather, albeit to a lesser extent.

SARS-CoV-2 versus other minor viral infection on kidney injury in asymptomatic and mildly symptomatic patients.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has become a global pandemic since December 2019. Most of the patients are mild or asymptomatic and recovered well as those suffered from other respiratory viruses. SARS-CoV-2 infection is supposed to demonstrate more sequelae. Acute kidney injury (AKI) is common among COVID-19 patients and is associated with disease severity and outcomes. Only a few studies focused on a detailed analysis of kidney damage in asymptomatic or mildly symptomatic COVID-19 patients. Whether any minor viral infection is likely to exhibit similar minor effect on renal function as COVID-19 is still unclear, and the definite pathophysiology of viral invasion is not fully understood. Currently, the proposed mechanisms of AKI include direct effects of virus on kidney, dysregulated immune response, or as a result of multi-organs failure have been proposed. This study will discuss the difference between COVID-19 and other viruses, focusing on proposed mechanisms, biomarkers and whether it matters with clinical significance.

Surveillance of adverse events following immunisation in Australia annual report, 2020.

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2020, reported to the Therapeutic Goods Administration (TGA), and describes reporting trends over the 21-year period from 1 January 2000 to 31 December 2020. There were 3,827 AEFI records for vaccines administered in 2020, an annual AEFI reporting rate of 14.9 per 100,000 population. There was a slight (3.8%) decrease in the overall AEFI reporting rate in 2020 compared with 2019 (15.5 per 100,000 population). This decrease in the AEFI reporting rate in 2020 is potentially due to the impact of coronavirus disease 2019 (COVID-19) and was mainly from a decline in reported adverse events related to HPV, dTpa, and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2020 were similar to 2019. The most commonly reported adverse events were injection site reaction (37.1%); pyrexia (18.1%); rash (15.8%); vomiting (7.6%); pain (7.4%); headache (5.7%); and urticaria (5.1%). There were six deaths reported to the TGA. In one of the reports, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining five reports, no clear causal relationship with vaccination was found.

Exploring the Chinese Public's Perception of Omicron Variants on Social Media: LDA-Based Topic Modeling and Sentiment Analysis.

The COVID-19 pandemic caused by SARS-CoV-2 is still raging. Similar to other RNA viruses, SARS-COV-2 is constantly mutating, which leads to the production of many infectious and lethal strains. For instance, the omicron variant detected in November 2021 became the leading strain of infection in many countries around the world and sparked an intense public debate on social media. The aim of this study is to explore the Chinese public's perception of the omicron variants on social media. A total of 121,632 points of data relating to omicron on Sina Weibo from 0:00 27 November 2021 to 23:59:59 30 March 2022 (Beijing time) were collected and analyzed with LDA-based topic modeling and DLUT-Emotion ontology-based sentiment analysis. The results indicate that (1) the public discussion of omicron is based on five topics, including omicron's impact on the economy, the omicron infection situation in other countries/regions, the omicron infection situation in China, omicron and vaccines and pandemic prevention and control for omicron. (2) From the 3 sentiment orientations of 121,632 valid Weibo posts, 49,402 posts were judged as positive emotions, accounting for approximately 40.6%; 47,667 were negative emotions, accounting for nearly 39.2%; and 24,563 were neutral emotions, accounting for about 20.2%. (3) The result of the analysis of the temporal trend of the seven categories of emotion attribution showed that fear kept decreasing, whereas good kept increasing. This study provides more insights into public perceptions of and attitudes toward emerging SARS-CoV-2 variants. The results of this study may provide further recommendations for the Chinese government, public health authorities, and the media to promote knowledge about SARS-CoV-2 variant pandemic-resistant messages.

Visualizing the Knowledge Base and Research Hotspot of Public Health Emergency Management: A Science Mapping Analysis-Based Study

Public health emergency management has been one of the main challenges of social sustainable development since the beginning of the 21st century. Research on public health emergency management is becoming a common focus of scholars. In recent years, the literature associated with public health emergency management has grown rapidly, but few studies have used a bibliometric analysis and visualization approach to conduct deep mining and explore the characteristics of the public health emergency management research field. To better understand the present status and development of public health emergency management research, and to explore the knowledge base and research hotspots, the bibliometric method and science mapping technology were adopted to visually evaluate the knowledge structure and research trends in the field of public health emergency management studies. From 2000 to 2020, a total of 3723 papers related to public health emergency management research were collected from the Web of Science Core Collection as research data. The five main research directions formed are child prevention, mortality from public health events, public health emergency preparedness, public health emergency management, and coronavirus disease 2019 (COVID-19). The current research hotspots and frontiers are climate change, COVID-19 and related coronaviruses. Further research is needed to focus on the COVID-19 and related coronaviruses. This study intends to contribute inclusive support to related academia and industry in the aspects of public health emergency management and public safety research, as well as research hotspots and future research directions.

COVID-19 vaccine development: milestones, lessons and prospects.

With the constantly mutating of SARS-CoV-2 and the emergence of Variants of Concern (VOC), the implementation of vaccination is critically important. Existing SARS-CoV-2 vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, and virus-like particle (VLP) vaccines. Viral vector vaccines, protein subunit vaccines, and mRNA vaccines may induce additional cellular or humoral immune regulations, including Th cell responses and germinal center responses, and form relevant memory cells, greatly improving their efficiency. However, some viral vector or mRNA vaccines may be associated with complications like thrombocytopenia and myocarditis, raising concerns about the safety of these COVID-19 vaccines. Here, we systemically assess the safety and efficacy of COVID-19 vaccines, including the possible complications and different effects on pregnant women, the elderly, people with immune diseases and acquired immunodeficiency syndrome (AIDS), transplant recipients, and cancer patients. Based on the current analysis, governments and relevant agencies are recommended to continue to advance the vaccine immunization process. Simultaneously, special attention should be paid to the health status of the vaccines, timely treatment of complications, vaccine development, and ensuring the lives and health of patients. In addition, available measures such as mix-and-match vaccination, developing new vaccines like nanoparticle vaccines, and optimizing immune adjuvant to improve vaccine safety and efficacy could be considered.

Research on Monetary Policy Implementation and Industrial Structure Transformation Under COVID-19-Evidence From Eight Economic Zones in Mainland China.

The outbreak of COVID-19 has brought a serious impact on the economies of various countries, monetary policy needs to play a role in stimulating economic recovery when the economy encounters a serious negative impact. Since the recurrent outbreak of COVID-19 has caused great obstacles to the normal economic exchanges between countries, it has become particularly important to build the domestic market and optimize the industrial allocation at this time. This paper focuses on studying the dynamic impact of China's monetary policy implementation on the industrial structure during the pandemic. Based on the data of the eight major economic zones in Mainland China and the dataset containing many of China's macroeconomic variables, a SV-TVP-FAVAR model is established. The manuscript compares the time-varying effects of monetary policy tools on the industries at different stages before and after the epidemic. The study supported some interesting conclusions. (1) Either the quantitative or price-based monetary policy shocks have significant time-varying impacts on the industries in different economic zones. The impacts of monetary policy on the primary, secondary, and tertiary industries in each economic zone are uneven. (2) The developed Northern, Eastern, and Southern coastal economic zones in Mainland China are more sensitive to the changes in monetary policy. (3) COVID-19 has brought a tremendous negative shock on the economy, which has destroyed the original steady-state of the economic system and added more uncertainty to the regulatory effect of monetary policy. Compared with other periods in China's economic history that severely negatively impacted (the Southeast Asian financial crisis and the global economic crisis), industries in most economic zones under the COVID-19 epidemic have been affected by monetary policy for a longer lag time. Therefore, for the implementation of monetary policy, at the moment of COVID-19 epidemic, we should pay more attention to the dual-pillar role of macro-prudential regulation, further improve the process of China's interest rate reform, enrich the monetary toolbox, and implement differentiated monetary policies in line with the economic zone's position, to optimize the regional industrial structure, and promote long-term economic growth.

Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti-SARS-CoV-2 Agents.

Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.