Rigidity of the outer shell predicted by a protein intrinsic disorder model sheds light on the COVID-19 (Wuhan-2019-nCoV) infectivity.

The human oral and gut commensal microbes play vital roles in the development and maintenance of immune homeostasis, while its association with susceptibility and severity of SARS-CoV-2 infection is barely understood. In this study, we investigated the dynamics of the oral and intestinal flora before and after the clearance of SARS-CoV-2 in 53 COVID-19 patients, and then examined their microbiome alterations in comparison to 76 healthy individuals. A total of 140 throat swab samples and 81 fecal samples from these COVID-19 patients during hospitalization, and 44 throat swab samples and 32 fecal samples from sex and age-matched healthy individuals were collected and then subjected to 16S rRNA sequencing and viral load inspection. We found that SARS-CoV-2 infection was associated with alterations of the microbiome community in patients as indicated by both alpha and beta diversity indexes. Several bacterial taxa were identified related to SARS-CoV-2 infection, wherein elevated Granulicatella and Rothia mucilaginosa were found in both oral and gut microbiome. The SARS-CoV-2 viral load in those samples was also calculated to identify potential dynamics between COVID-19 and the microbiome. These findings provide a meaningful baseline for microbes in the digestive tract of COVID-19 patients and will shed light on new dimensions for disease pathophysiology, potential microbial biomarkers, and treatment strategies for COVID-19.

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.

The pandemic of coronavirus disease 2019 (COVID‐19) is continually worsening. Clinical treatment for COVID‐19 remains primarily supportive with no specific medicines or regimens. Here, the development of multifunctional alveolar macrophage (AM)‐like nanoparticles (NPs) with photothermal inactivation capability for COVID‐19 treatment is reported. The NPs, made by wrapping polymeric cores with AM membranes, display the same surface receptors as AMs, including the coronavirus receptor and multiple cytokine receptors. By acting as AM decoys, the NPs block coronavirus from host cell entry and absorb various proinflammatory cytokines, thus achieving combined antiviral and anti‐inflammatory treatment. To enhance the antiviral efficiency, an efficient photothermal material based on aggregation‐induced emission luminogens is doped into the NPs for virus photothermal disruption under near‐infrared (NIR) irradiation. In a surrogate mouse model of COVID‐19 caused by murine coronavirus, treatment with multifunctional AM‐like NPs with NIR irradiation decreases virus burden and cytokine levels, reduces lung damage and inflammation, and confers a significant survival advantage to the infected mice. Crucially, this therapeutic strategy may be clinically applied for the treatment of COVID‐19 at early stage through atomization inhalation of the NPs followed by NIR irradiation of the respiratory tract, thus alleviating infection progression and reducing transmission risk.