A cosmetic method for modulating pigmentation in a subject includes administering a modulator of angiotensin-converting enzyme 2 (ACE2 modulator) to the subject. The ACE2 modulator can be an inhibitor of angiotensin-converting enzyme 2 (ACE2 inhibitor), in which case, the ACE2 inhibitor can be administered to increase pigmentation in the subject. The ACE2 modulator can also be an activator of angiotensin-converting enzyme 2 (ACE2 activator), in which case the ACE2 activator can be administered to decrease pigmentation in the subject. The treatment of inflammatory skin disease can also be achieved by inhibition of angiotensin-converting enzyme 2.

Disclosed are compounds, compositions, and methods for treating and/or preventing infection by viruses that utilize the angiotensin converting enzyme 2 (ACE2) as a cellular receptor such as sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Particularly disclosed are recombinant ACE2-Fc fusion proteins and ACE2 variants that exhibit anti-SARS-CoV-2 binding activity and decouple anti-SARS-CoV-2 activity from side effects such as cardiovascular effects, where the fusion proteins and variants exhibit reduced ACE2 enzymatic activity.

This disclosure is directed to inhibitory oligonucleotides, inhibitory peptides, compositions and methods for preventing or treating Coronavirus disease 2019 (COVID-19). In one aspect, the disclosure is directed to compositions that comprise inhibitory oligonucleotides against one or more SARS-CoV-2 virus genes. In another aspect, the disclosure is directed to compositions that comprise inhibitory peptides that inhibit SARS-COV-2 entry into cells. Another aspect of the disclosure is directed to gene therapy methods for treating COVID-19, and vectors for carrying out the same. Finally, the disclosure provides nutritional supplements to support human immunity and prevent or inhibit viral infections.

This disclosure describes recombinant angiotensin-converting enzyme II (ACE2) polypeptides, fusion proteins, and compositions thereof having improved binding affinity for the SARS-CoV-2 spike protein receptor binding domain relative to wild-type ACE2. Also provided are methods of using the recombinant ACE2 polypeptides, fusion proteins, and compositions thereof for treating subjects infected with a SARS-CoV-2 virus (i.e., subjects with COVID-19), subjects having symptoms suggestive of a SARS-CoV-2 infection, and subjects exposed to or at risk of exposure to SARS-CoV-2 virus. Other virus infections may also be treated.

The present disclosure provides a transgenic, immunocompromised mouse engineered to express a human angiotensin converting enzyme 2 (huACE2) sequence. The huACE2 sequence may be operably linked to a human keratin 18 (hKRT18) promoter or the endogenous mouse angiotensin converting enzyme 2 (mACE2) promoter. Transgenic immunocompromised mice of the present disclosure may be utilized in methods of evaluating a test agent for reducing or preventing SARS-CoV-2 infection.

Peptide-E3 ubiquitin ligase fusions representing minimal protein to proteasome linkers are specifically targeted to degrade endogenous FOXP3 proteins in regulatory T cells. An engineered peptide for functional inactivation of a target regulatory T cell includes a fusion protein comprising a targeting domain and a ubiquitin ligase recruiting domain, wherein the targeting domain is engineered to bind FOXP3 of the target regulatory T cell for mediated degradation by the ubiquitin-proteosome pathway. The targeting domain may comprise a peptide having amino acid [SEQ ID No. 3], [SEQ ID No. 4], [SEQ ID No. 5], [SEQ ID No. 6], or [SEQ ID No. 7]. The ubiquitin ligase recruiting domain recruits an E3 ubiquitin ligase, which may be CHIPΔTPR [SEQ ID No. 2]. An engineered minimal, specific, nucleotide-encodable, FOXP3 protein to proteasome linker comprises a peptide-E3 ubiquitin ligase fusion in which the peptide binds to FOXP3. A method for treatment includes administering to a subject an engineered peptide-based therapeutic or pharmaceutically acceptable salt thereof, wherein the engineered peptide-based therapeutic comprises a peptide fusion of a targeting domain and a ubiquitin ligase recruiting domain, and wherein the targeting domain is engineered to bind FOXP3 of at least one regulatory T cell for mediated degradation by the ubiquitin-proteosome pathway.

Provided herein are multivalent particles and compositions of multivalent particles for blocking viral infection.

A fusion protein, comprising a variant angiotensin converting enzyme 2 (ACE2) domain covalently fused to a Fc domain. The variant ACE2 domain has a N-terminal deletion, a C-terminal deletion, or both, relative to a full-length wildtype ACE2 having a SEQ ID NO: 1. The variant ACE2 domain has ACE2 activity.

This disclosure is directed to inhibitory oligonucleotides, inhibitory peptides, compositions and methods for preventing or treating Coronavirus disease 2019 (COVID-19). In one aspect, the disclosure is directed to compositions that comprise inhibitory oligonucleotides against one or more SARS-CoV-2 virus genes. In another aspect, the disclosure is directed to compositions that comprise inhibitory peptides that inhibit SARS-COV-2 entry into cells. Another aspect of the disclosure is directed to gene therapy methods for treating COVID-19, and vectors for carrying out the same. Finally, the disclosure provides nutritional supplements to support human immunity and prevent or inhibit viral infections.

Disclosed are small peptides derived from the binding interface of each of SARS-CoV-2 spike protein and ACE2 receptor, compositions comprising the same, and prophylactic and therapeutic uses of the peptides and the compositions. Also disclosed is a novel protocol of identifying, designing, and modifying the small peptides based on computer simulation.