Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 29, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2102957118
Keywords
SARS-CoV-2; virus inhibitor; hACE2-containing nanocatchers; inhalation; mucoadhesive
Categories
Funding
- National Research Programs of China [2016YFA0201200, 2020YFA0211100]
- National Natural Science Foundation of China [91959104, 21927803, 51903182, 51525203]
- Natural Science Foundation of Jiangsu Province [BK20190826]
- National Facility for Translational Medicine (Shanghai) [TMSK2020012]
- China Postdoctoral Science Foundation [2020M671583]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- 111 Program from the Ministry of Education of China
- Emergency Research Project of COVID-19 from Zhejiang University
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Amid the global COVID-19 pandemic caused by SARS-CoV2, scientists have developed a novel approach to combat the virus, by designing hACE2-containing nanocatchers to protect cells from infection and potentially provide an alternative treatment option. This innovative method shows promising results in inhibiting SARS-CoV-2 infections, including mutated strains, and offers great potential for future clinical use in the ongoing epidemic.
The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.
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