The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro with IC50 values ranging from 7.6 to 748.5 nM. The co-crystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a SARS-CoV-2 infection transgenic mouse model, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.
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Messenger RNA (mRNA) vaccines to prevent COVID-19 have made headlines around the world recently, but scientists have also been working on mRNA vaccines to treat or prevent other diseases, including some forms of cancer. Now, researchers reporting in ACS
Nano Letters have developed a hydrogel that, when injected into mice with melanoma, slowly released RNA nanovaccines that shrank tumors and kept them from metastasizing.
Cancer immunotherapy vaccines work similarly to mRNA vaccines for COVID-19, except they activate the immune system to attack tumors instead of a virus. These vaccines contain mRNA that encodes proteins made specifically by tumor cells. When the mRNA enters antigen-presenting cells, they begin making the tumor protein and displaying it on their surfaces, triggering other immune cells to seek and destroy tumors that also make this protein. However, mRNA is an unstable molecule that is quickly degraded by enzymes in the body. For cancer immunotherapy, rese
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