Pharmacological treatments based on the RAS blockade are used extensively for the treatment of hypertension and CV remodeling. However, in spite of their success in pharmacological blockade of the RAS, the prevalence of end-organ damage has risen steadily in the last several decades. These observations indicate that novel and innovative approaches must be used in an attempt to promote a more effective treatment for the residual CV remodeling. In this environment, the ACE2/Ang-(1-9) axis is an important target, that is critical in tipping the balance of vasoconstrictive/proliferative to vasodilatory/antiproliferative axis of the RAS. Conceptually, the ACE2/Ang-(1-9)/AT2 axis balances the adverse effects of the ACE-Ang II-AT1 receptor axis ( Figure 3 ). Accumulating evidence suggests that ACE2 expression and Ang-(1-9) levels are altered in diastolic and systolic dysfunction and remodeling and the activation of the ACE2/Ang-(1-9) axis protects the heart and vessels from cardiovascular remodeling. In conclusion, the noncanonical RAS arm has new biological effector Ang-(1-9) to counterregulate the classical RAS. Viral Proteins Acquired from a Host Converge to Simplified Domain Architectures The infection cycle of viruses creates many opportunities for the exchange of genetic material with the host. Many viruses integrate their sequences into the genome of their host for replication. These processes may lead to the virus acquisition of host sequences. Such sequences are prone to accumulation of mutations and deletions. However, in rare instances, sequences acquired from a host become beneficial for the virus. We searched for unexpected sequence similarity among the 900,000 viral proteins and all proteins from cellular organisms. Here, we focus on viruses that infect metazoa. The high-conservation analysis yielded 187 instances of highly similar viral-host sequences. Only a small number of them represent viruses that hijacked host sequences. The low-conservation sequence analysis utilizes the Pfam family collection. About 5% of the 12,000 statistical models archived in Pfam are composed of viral-metazoan proteins. In about half of Pfam families, we provide indirect support for the directionality from the host to the virus. The other families are either wrongly annotated or reflect an extensive sequence exchange between the viruses and their hosts. In about 75% of cross-taxa Pfam families, the viral proteins are significantly shorter than their metazoan counterparts. The tendency for shorter viral proteins relative to their related host proteins accounts for the acquisition of only a fragment of the host gene, the elimination of an internal domain and shortening of the linkers between domains. We conclude that, along viral evolution, the host-originated sequences accommodate simplified domain compositions. We postulate that the trimmed proteins act by interfering with the fundamental function of the host including intracellular signaling, post-translational modification, protein-protein interaction networks and cellular trafficking. We compiled a collection of hijacked protein sequences. These sequences are attractive targets for manipulation of viral infection. Many studies, mainly from bacteria and unicellular eukaryotes, focus on the exchange of genetic material between viruses and cellular hosts. Sequences are best studied through their structural and functional domains [1, 2, 3, 4, 5] . The evolution of domains is a significant force for shaping the proteins along the tree of life. Sequence exchange between genomes within and between superkingdoms is evident from the appearance of a domain in a particular phylogenetic branch [6] . The contribution of horizontal gene transfer is not limited to bacteria but has occurred across distant species [3] . For example, some signaling domains in bacteria are the consequence of a horizontal gene transfer [7] .