Automatically switches editor shortcut profile when playing. Based on https://gist.github.com/RodGreen/8d5f5452c459755d9bf6bad1015ef194

PlayModeShortcutManagerProfileUtility.cs

using System;
using System.Linq;
using UnityEditor;
using UnityEditor.ShortcutManagement;
using UnityEngine;

[InitializeOnLoad]
public class PlayModeShortcutManagerProfileUtility
{
    #region Types

    private class PlayModeShortcutProfileScope : IDisposable
    {
        #region Fields

        private readonly string _lastEditModeProfile;

        private bool _disposed;

        #endregion

        #region Constructors

        public PlayModeShortcutProfileScope()
        {
            var shortcutManager = ShortcutManager.instance;
            _lastEditModeProfile = shortcutManager.activeProfileId;
            if (HasPlayModeProfile)
            {
                shortcutManager.activeProfileId = PLAY_MODE_PROFILE_ID;
            }
            else
            {
                Debug.LogError($"Missing Shortcut Manager profile '{PLAY_MODE_PROFILE_ID}'. Will recreate on next recompile.");
            }
        }

        #endregion

        #region Methods

        /// <inheritdoc />
        public void Dispose()
        {
            if (_disposed)
            {
                throw new InvalidOperationException("Object is already disposed.");
            }

            _disposed = true;
            ShortcutManager.instance.activeProfileId = _lastEditModeProfile;
        }

        #endregion
    }

    #endregion

    #region Fields

    private const string PLAY_MODE_PROFILE_ID = "Play Mode";

    private static readonly string[] _ignoredIdPrefixes =
    {
        "3D Viewport/",
        "Window/Fullscreen Game View",
        "Main Menu/Edit/Step",
        "Main Menu/Edit/Pause"
    };

    private static PlayModeShortcutProfileScope _lastScope;

    #endregion

    #region Properties

    private static bool HasPlayModeProfile
    {
        get
        {
            var shortcutManager = ShortcutManager.instance;
            var allProfiles = shortcutManager.GetAvailableProfileIds();
            return allProfiles.Contains(PLAY_MODE_PROFILE_ID);
        }
    }

    #endregion

    #region Constructors

    static PlayModeShortcutManagerProfileUtility()
    {
        EditorApplication.playModeStateChanged += OnPlayModeStateChanged;
        EditorApplication.delayCall += CreatePlayModeProfile;
    }

    #endregion

    #region Methods

    private static void CreatePlayModeProfile()
    {
        if (HasPlayModeProfile)
        {
            return;
        }

        var shortcutManager = ShortcutManager.instance;
        shortcutManager.CreateProfile(PLAY_MODE_PROFILE_ID);

        // Ensure playmode profile is (almost) completely empty
        using (new PlayModeShortcutProfileScope())
        {
            foreach (var shortcutId in shortcutManager.GetAvailableShortcutIds())
            {
                var shouldIgnore = false;
                foreach (var prefix in _ignoredIdPrefixes)
                {
                    if (shortcutId.StartsWith(prefix))
                    {
                        shouldIgnore = true;
                        break;
                    }
                }

                if (shouldIgnore)
                {
                    continue;
                }

                if (shortcutManager.IsShortcutOverridden(shortcutId))
                {
                    shortcutManager.ClearShortcutOverride(shortcutId);
                }

                shortcutManager.RebindShortcut(shortcutId, ShortcutBinding.empty);
            }
        }
    }

    private static void OnPlayModeStateChanged(PlayModeStateChange state)
    {
        switch (state)
        {
            case PlayModeStateChange.EnteredPlayMode:
            {
                SetUsePlayModeProfile(true);
                break;
            }
            case PlayModeStateChange.EnteredEditMode:
            {
                SetUsePlayModeProfile(false);
                break;
            }
        }
    }

    private static void SetUsePlayModeProfile(bool use)
    {
        _lastScope?.Dispose();
        _lastScope = default;
        if (use)
        {
            _lastScope = new PlayModeShortcutProfileScope();
        }
    }

    #endregion
}