Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

Perforación intestinal causada por COVID-19 / Intestinal perforation caused by COVID-19 / Perfuração intestinal causada por COVID-19

Resumen: A medida que la pandemia por el virus SARS-CoV-2 se propaga por todo el mundo, se informan nuevas manifestaciones clínicas. Además de las manifestaciones respiratorias, se han descrito lesión renal aguda, hipercoagulabilidad, tromboembolia pulmonar y síntomas gastrointestinales. En el Hospital de Infectología del Centro Médico Nacional La Raza, en la Unidad de Cuidados Intensivos se han atendido 148 pacientes de noviembre de 2020 a noviembre de 2021 por COVID-19 de severo a crítico. Presentamos un caso de paciente con SARS-CoV-2 con perforación intestinal por congestión vascular a nivel del ciego por COVID-19 crítico.

Abstract: As the SARS-CoV-2 virus pandemic spreads around the world, new clinical manifestations are being reported. In addition to respiratory manifestations, acute kidney injury, hypercoagulability, pulmonary thromboembolism, and gastrointestinal symptoms have been described. The Hospital de Infectología del Centro Médico Nacional La Raza, in the Intensive Care Unit, has treated 148 patients from November 2020 to November 2021 for COVID-19 from severe to critical. We present the case of a patient with SARS-CoV-2, with intestinal perforation due to vascular congestion at the level of the cecum in a critical COVID-19 patient.

Resumo: À medida que a pandemia do vírus SARS-CoV-2 se espalha pelo mundo, novas manifestações clínicas estão sendo relatadas. Além das manifestações respiratórias, foram descritos lesão renal aguda, hipercoagulabilidade, tromboembolismo pulmonar e sintomas gastrointestinais. O Hospital de Infectologia do Centro Médico Nacional «La Raza¼, na Unidade de Terapia Intensiva, tratou 148 pacientes de novembro de 2020 a novembro de 2021 para COVID-19 de estado grave a crítico. Apresentamos o caso de um paciente com SARS-CoV-2, com perfuração intestinal por congestão vascular ao nível do ceco em um paciente em estado crítico com COVID-19.

Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed

Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.

Bioactive natural compounds against human coronaviruses: a review and perspective

Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19.