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This paper addresses the stability of plane Couette flow in the presence of strong density and viscosity stratifications. It demonstrates the existence of a generalised inflection point that satisfies the generalised Fjortoft's criterion of instability when a minimum of kinematic viscosity is present in the base flow. The characteristic scales associated with this minimum are identified as the primary controlling parameters of the associated instability, regardless of the type of stratification. To support this finding, analytical stability models are derived in the long wave approximation using piecewise linear base flows. Numerical stability calculations are carried out to validate these models and to provide further information on the production of disturbance vorticity. All instabilities are interpreted as arising from the interaction between two vorticity waves. Depending on the type of stratification, these two waves are produced by different physical mechanisms. When both strong density and viscosity stratifications are present, we show that they result from the concurrent action of shear and inertial baroclinic effects. The stability models developed for simple fluid models ultimately shed light on a recently observed unstable mode in supercritical fluids (Ren et al., J. Fluid Mech., vol. 871, 2019, pp. 831-864), providing a quantitative prediction of the stability diagram and identifying the dominant mechanisms at play. Furthermore, our study suggests that the minimum of kinematic viscosity reached at the Widom line in these fluids is the leading cause of their instability. The existence of similar instabilities in different fluids and flows (e.g., miscible fluids) is finally discussed.