The disclosure provides helix grafted proteins, methods of producing helix grafted proteins and methods of use of helix grafted proteins as inhibitors of protein-protein interactions involved in disease pathogenesis.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

The present application discloses in detail mutant ligands of the human G protein alpha-subunit -Gi1-, wherein at least one amino acid residue has been replaced with alanine if the at least one amino acid residue is a non-alanine residue, or at least one amino acid residue has been replace with glycine if the at least one amino acid residue is alanine and wherein the at least one amino acid residue is comprised in a first group containing of the amino acid residues with position R32A, K54A, I55A, I56A, H57A, R176A, E245A, Y296A, T327A, N331A, V332A and D350A or is comprised in a second group containing G42A, A59G, T177A, D200A, A226G, E297A, A300G and F334A or is comprised in a third group containing V50A, A59G, R178A 30 and K180A.

Resonance energy transfer (RET)- or protein-fragment complement assay (PCA)-based biosensors useful for assessing the activity of G-proteins are described. These biosensors are based on the competition between the G subunit and a G interacting protein ( IP) for the binding to the G dimer. These biosensors comprises (1) a IP and (2) a G or G protein; a GPCR; or a plasma membrane targeting domain, fused to suitable RET or PCA tags. Methods using such biosensors for different applications, including the identification of agents that modulates G-protein activity or for the characterization of GPCR signaling/regulation, such as G-protein preferences and activation profiles of GPCRs, are also described.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Provided herein are compounds that inhibit a binding interaction between a integrin and a G protein subunit, as well as compositions, e.g., pharmaceutical compositions, comprising the same, and related kits. In some embodiments, the compound is an antibody or antibody analog, and, in other embodiments, the compound is a peptide or peptide analog. Also provided are methods of using the compounds, including methods of treating or preventing a medical condition, such as stroke, heart attack, cancer, or inflammation.

An purpose of the present invention is to provide a construct for expressing a G protein-coupled receptor, and the use of said construct. The construct is used for expressing a G protein-coupled receptor protein or a subunit thereof, wherein the construct is characterized by including a nucleic acid that encodes G protein subunit protein; a nucleic acid that comprises an IRES sequence; and a nucleic acid that encodes the G protein-coupled receptor protein or a subunit thereof in the stated order from the 5 side in a single vector.

The present disclosure relates to the field of G protein coupled receptor (GPCR) structural biology and signaling. In particular, the present disclosure relates to binding domains directed against and/or specifically binding to GPCR:G protein complexes. Also provided are nucleic acid sequences encoding such binding domains and cells expressing or capable of expressing such binding domains. The binding domains of the present disclosure can be used as universal tools for the structural and functional characterization of G-protein coupled receptors in complex with downstream heterotrimeric G proteins and bound to various natural or synthetic ligands, for investigating the dynamic features of G protein activation, as well as for screening and drug discovery efforts that make use of GPCR:G protein complexes.

The invention provides a mutant of a parent heterotrimeric G protein alpha (G) subunit, which mutant (i) lacks at least one helix of the helical domain of the parent G subunit; (ii) is capable of binding to a GPCR in the absence of a heterotrimeric G protein beta (G) subunit and a heterotrimeric G protein gamma (G) subunit; and (iii) has an amino acid sequence that contains one or more mutations compared to the amino acid sequence of the parent heterotrimeric G subunit, which mutations are selected from a deletion, a substitution and an insertion.

Methods, compositions and kits for regulating complement activity or treating a complement activity disorder in a subject using soluble, membrane-independent CD59 protein, methods of assaying human macular degeneration (MD), and methods and kits for assaying potential therapeutic agents for treatment of human MD are provided herein.