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Review
. 2021 Mar 18;10(3):e1240.
doi: 10.1002/cti2.1240. eCollection 2021.

RGD-binding integrins and TGF-β in SARS-CoV-2 infections - novel targets to treat COVID-19 patients?

Ingrid Carvacho  1 , Matthias Piesche  2   3
Affiliations
Review

RGD-binding integrins and TGF-β in SARS-CoV-2 infections - novel targets to treat COVID-19 patients?

Ingrid Carvacho et al. Clin Transl Immunology. .

Abstract

The new coronavirus SARS-CoV-2 is a global pandemic and a severe public health crisis. SARS-CoV-2 is highly contagious and shows high mortality rates, especially in elderly and patients with pre-existing medical conditions. At the current stage, no effective drugs are available to treat these patients. In this review, we analyse the rationale of targeting RGD-binding integrins to potentially inhibit viral cell infection and to block TGF-β activation, which is involved in the severity of several human pathologies, including the complications of severe COVID-19 cases. Furthermore, we demonstrate the correlation between ACE2 and TGF-β expression and the possible consequences for severe COVID-19 infections. Finally, we list approved drugs or drugs in clinical trials for other diseases that also target the RGD-binding integrins or TGF-β. These drugs have already shown a good safety profile and, therefore, can be faster brought into a trial to treat COVID-19 patients.

Keywords: ARDS; COVID‐19; RGD‐binding integrins; TGF‐β; cytokines; inflammation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Schematic representation of SARS‐CoV‐2 S‐protein with a focus on the receptor‐binding domain. The sequences of the spike protein of human SARS‐CoV‐2, human SARS‐CoV‐1 (75% similarity) and bat RaTG13 (96% similarity) were aligned using MAFFT. 176 The receptor‐binding domain and the ACE2 receptor‐binding region are coloured in light blue. The RGD motif of SARS‐CoV‐2 is highlighted in red. Numbers refer to the SARS‐CoV‐2 spike protein sequence. FP, fusion peptide; RGD, amino acids arginine‐glycine‐aspartic acid; S1, subunit of spike; S2, subunit of spike (fusion domain); S2´, cleavage site; TM, transmembrane domain.
Figure 2
Figure 2
Multiple conditions lead to higher levels TGF‐β. Representation of medical conditions that are associated to high levels of TGF‐β. These can be related to the severe cases of COVID‐19. Specific inhibition of TGF‐β mechanism of action could prevent severe COVID‐19 symptoms. COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis; CF, cystic fibrosis.
Figure 3
Figure 3
Scheme representing the potential effect of RGD‐binding integrin inhibitors to avoid the common complications derived from SARS‐CoV‐2 infection.
See this image and copyright information in PMC

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