Researchers around the world are in an urgent race to find an effective therapy for COVID-19. It is becoming undeniably evident that in addition to an efficacious vaccine, the development of therapeutics is necessary to completely end this pandemic and provide a solution to treat COVID-19 patients who are severely ill. Therefore, initial efforts to combat the virus primarily focused on containment to stop the spread and elucidate the pathogenesis of the virus. Similar to its deadly predecessors, SARS-CoV-1 (the cause of SARS in 2003) and Middle East respiratory syndrome (MERS)-CoV (the cause of MERS in 2012), SARS-CoV-2 is an enveloped, positive-sense, β coronavirus with dangerously high human-to-human transmission rates, with a reported R 0 (the average number of people that one contagious person will infect) ranging from 2 to 6 (refs.
SARS-CoV-2 is capable of wreaking havoc on the respiratory and immune system by inducing secretion of proinflammatory cytokines, thereby triggering an increase in alveolar oedema, hypoxaemia, dyspnoea and systemic inflammatory response syndrome 2. Rarely, more severe and lethal forms emerge. Coronaviruses are a common type of virus: alpha (α) coronaviruses and beta (β) coronaviruses can infect mammals and often manifest as the common cold or gastrointestinal discomfort. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen at the centre of the current global pandemic, causes coronavirus disease 2019 (COVID-19) 1. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19. In cynomolgus macaques challenged with live SARS-CoV-2, four doses of these nanodecoys delivered by inhalation promoted viral clearance and reduced lung injury. Furthermore, inhalation of the LSC-nanodecoys accelerated clearance of SARS-CoV-2 mimics from the lungs, with no observed toxicity. In mice, these LSC-nanodecoys were delivered via inhalation therapy and resided in the lungs for over 72 h post-delivery. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection.
Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date.
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