The present disclosure relates to recombinant fusion proteins comprising an extracellular domain of the human angiotensin-converting enzyme 2 (ACE2), optionally having altered amino acid residues that result in increased binding affinity for the S1 spike protein of SARS-CoV-2, linked to a human immunoglobulin Fc region, that can extend the protein half-life (T.sub.1/2) and/or the duration of action as a decoy receptor, and compositions and methods of use of these fusion proteins.

Methods and compositions relating to an engineered peptide capable of binding to a biological molecule for viral inhibition. The engineered peptide is computationally-derived from soluble angiotensin-converting enzyme 2 (sACE2), a known receptor for viral spike proteins. The engineered peptide is optimized for minimal size and off-target effects. The engineered sACE2 peptide variants are a suitable targeting domain for fusion proteins of various effects.

Disclosed herein are peptide sequences capable of directing adeno-associated viruses (AAV) to target specific environments, for example the nervous system and the heart, in a subject. Also disclosed are AAVs having non-naturally occurring capsid proteins comprising the disclosed peptide sequences, and methods of using the AAVs to treat diseases.

The present invention provides polypeptides with coronavirus neutralising capacity. It further provides nucleic acids, vectors, cells, pharmaceutical compositions and medical uses that exploit the polypeptides of the invention

Compositions and methods are described for the delivery of therapeutic products (such as therapeutic proteins (for example, antibodies), therapeutic RNAs (for example, shRNAs, siRNAs, and miRNAs), and therapeutic aptamers) to the retina/vitreal humour in the eyes of human subjects to treat pathologies of the eye, involving, for example, recombinant viral vectors such as recombinant adeno-associated virus (rAAV) vectors.

A method of preventing, reducing a risk of, or treating a virus infection, or preventing or treating a symptom caused by the virus in a subject, said method comprising administering to said subject an effective amount of a fusion protein, wherein the fusion protein comprises a variant angiotensin converting enzyme 2 (ACE2) domain covalently fused to a Fc domain. The variant ACE2 domain comprises a N-terminal deletion, a C-terminal deletion, or both, relative to a full-length wildtype ACE2 having a SEQ ID NO. 1, and the variant ACE2 domain has ACE2 activity. The virus may be SARS-CoV, SARS-CoV-2, or MERS-CoV. The symptom comprises Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Acute Respiratory Distress Syndrome (ARDS), Pulmonary Arterial Hypertension (PAH), or Coronavirus Disease 2019 (COVID-19).

Provided is a method for preventing or treating a metabolic disorder, including administering to a subject a therapeutically effective amount of TRABID protein or a functionally related variant thereof, or a nucleic acid encoding TRABID protein or a functionally related variant thereof. Also provided is a method for reducing fat accumulation through TRABID-induced deubiquitination to promote autophagy activity and lipid metabolism.

Disclosed herein, in certain embodiments, are methods and compositions for treatment of acute respiratory distress syndrome (ARDS) induced by, inter alia, viral agents, comprising administration of fibroblasts, and/or fibroblast derivatives, and/or fibroblast apoptotic bodies. In one embodiment, a patient infected with coronavirus (COVID19) ARDS is administered a concentration of fibroblasts, intravenously, ranging from 10,000 fibroblasts to 300 million fibroblasts, based on patient characteristics and cause of ARDS. In some embodiments, fibroblasts are administered in a non-activated form, whereas in other embodiments, fibroblasts are treated under conditions stimulating enhanced activities beneficial to treatment of ARDS.

A mutant soluble human Ace2 (hAce2) protein useful in preventing infection with betacoronaviruses, including SARS-CoV2 is provided, as are compositions useful in treating disease associated with betacoronavirus, including, e.g, COVID-19. Also provided are compositions containing same formulated for intranasal and/or intrapulmonary delivery, methods of making same and assays. The use of the rAAV compositions for preventing symptoms of COVID-19 infection in humans is provided.

Provided herein are methods of treating Neuronal Ceroid Lipofuscinosis (CLN2) disease in a subject less than 3 years old. In exemplary embodiments, the method comprises administering to the subject a formulation comprising recombinant human tripeptidyl peptidase-1 (rhTPP1) in an amount effective to treat the CLN2 disease in the subject. Also provided are methods of delaying the onset of CLN2 disease, or a symptom thereof, in a subject less than 3 years old. In exemplary embodiments, the method comprises administering to the subject a formulation comprising recombinant human tripeptidyl peptidase-1 (rhTPP1) in an amount effective to delay the onset of the CLN2 disease or symptom in the subject.