SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications

Abstract

The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. Using the STRING bioinformatic tool and references through text mining tools associated to Coronaviruses, we identified SAMHD1 as the probable link to neurological symptoms. Paralleled to the response to influenza A virus and, specifically, respiratory syncytial virus, SARS-CoV-2 evokes a response that needs robust induction of a subclass of cytokines, including the Type I and, obviously, Type III interferons as well as a few chemokines. We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway. No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP. We suggest that SAMHD1 is the molecule that may be behind the mechanisms of the neurological complications associated with COVID-19.

The Method and Results of a Treatment Targeting SARS-CoV-2-Activated Inflammasomes

“…Furthermore, NRP1 is a host factor for the entry of SARS-CoV-2 into the brain through the olfactory epithelium [37]. SARS-CoV-2 evokes a response that needs strong induction of a subclass of cytokines, including type I and, obviously, type III interferons and a few chemokines, such as the response to in uenza A virus and, speci cally, respiratory syncytial virus [14,38].…”

“…After RNA virus infection, NLRP3 in ammasomes are activated by the mitochondrial protein mitofusin 2 [13]. Mitochondrial antiviral signalling protein (MAVS) with NLRP3 and SAMHD1 (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1) are linked to the NF-kB pathway [14] and NLRP3 to regulate in ammasome activity [15]. The following guidelines for COVID-19 acute respiratory distress syndrome (ARDS) as an indication were established.…”

Specific Treatment exists for SARS-CoV-2 ARDS

“…Furthermore, NRP1 is a host factor for the entry of SARS-CoV-2 into the brain through the olfactory epithelium 42 . SARS-CoV-2 evokes a response that needs strong induction of a subclass of cytokines, including type I and, obviously, type III interferons and a few chemokines, such as the response to in uenza A virus and, speci cally, respiratory syncytial virus 14,43 . SAMHD1 links to the NF-kB pathway 14 .…”

“…SARS-CoV-2 evokes a response that needs strong induction of a subclass of cytokines, including type I and, obviously, type III interferons and a few chemokines, such as the response to in uenza A virus and, speci cally, respiratory syncytial virus 14,43 . SAMHD1 links to the NF-kB pathway 14 . Now, we can correlate ACE2, NRP1, and SAMHD1 with the neurologic complications of COVID-19.…”

“…After RNA virus infection, NLRP3 in ammasomes are activated by the mitochondrial protein mitofusin 2 13 . Mitochondrial antiviral signalling protein (MAVS) with NLRP3 and SAMHD1 (SAM and HD domain-containing deoxynucleoside triphosphate triphosphohydrolase 1) are linked to the NF-kB pathway 14 . Also, NLRP3 is able to regulate in ammasome activity 15 .…”